Background: The current standard technique for vascular grafting in cerebral revascularization surgery is through the interposition of an autologous blood vessel. Technical complications have necessitated the development of a synthetic alternative, but classical biomaterials are not suited for small caliber vascular grafting due to neointimal hyperplasia and thrombosis. Electrospinning of polymers is a promising technique for the development of small vascular grafts. The in vivo performance and efficacy of electrospun polyurethane (ePU) grafts with an internal diameter of < 1.5 mm have thus far not been evaluated. Methods: We developed a novel ePU graft with a diameter of 1.25 mm for implantation into the infrarenal aorta of rats. Results: Patency rates of grafts after a four-month-period were equal to those reported in other studies with larger ePU graft diameters, and equal or higher than in studies with other biomaterials. We observed some loss in flow velocity throughout the grafts, which suggests a decreased elasticity of the graft compared to native rat aorta. However, the grafts demonstrated good neo-endothelialization and minimal neointimal hyperplasia. Their porosity promoted cellular infiltration, as shown on tissue slide examination. Conclusion: Our results show that ePU vascular grafts with internal diameter of < 1.5 mm are promising candidates for vascular grafting in cerebral revascularization surgery.

Background: Hypopituitarism is a potentially serious but often underdiagnosed condition that can occur following non-traumatic subarachnoid hemorrhage (SAH). The condition is characterized by the partial or complete deficiency of one or more pituitary hormones, leading to a range of clinical manifestations that may complicate the recovery process. This narrative review aims to synthesize the current literature on the prevalence, pathophysiology, and clinical implications of hypopituitarism associated with non-traumatic SAH. Methods: A comprehensive review of the literature was conducting by authors using databases such as PubMed, MEDLINE, and Scopus, focusing on studies published in the last two decades. Studies were selected based on their relevance to the topic, with an emphasis on those that reported on the prevalence, diagnostic approaches, pathophysiological mechanisms, and clinical outcomes of hypopituitarism post-SAH. Results: The review revealed a wide variability in the reported prevalence of hypopituitarism following non-traumatic SAH, ranging from 14% to 92.3%, depending on the diagnostic criteria, timing of assessment, and hormonal axes evaluated. Commonly affected hormones include growth hormone, gonadotropins, and cortisol. The pathophysiology of hypopituitarism in this context is multifactorial, involving ischemic damage, inflammation, and direct mechanical injury to the hypothalamic-pituitary axis. While some studies suggest a link between hypopituitarism and adverse clinical outcomes, the evidence remain inconclusive, highlighting the need for standardized diagnostic protocols and longitudinal studies. Conclusion: Hypopituitarism is a prevalent but often overlooked complication of non-traumatic SAH, with significant potential implications for long-term health outcomes. Routine endocrine evaluation and management of pituitary deficiencies are recommended to improve patient care. Future research should focus on refining diagnostic criteria, elucidating the underlying mechanisms, and evaluating the long-term impact of hormone replacement therapy in this patient population.

Alzheimer’s Disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of extracellular amyloid-β peptides (Aβ) within the cerebral parenchyma and vasculature, the latter termed cerebral amyloid angiopathy (CAA). This study utilized confocal imaging to investigate heparan sulfate (HS) within the cerebrovasculature and its potential associations with CAA, gender, and ApoE4 genotype. Our investigation revealed elevated levels of HS in the cerebrovasculature of AD patients with severe CAA. Additionally, these patients exhibited higher colocalization of HS with Aβ in the cerebrovasculature, including both endothelial and vascular smooth muscle cell compartments. Intriguingly, a reversal in the polarized expression of HS within the cerebral vasculature was detected in AD patients with severe CAA, suggesting a potential role in CAA development. Furthermore, male patients exhibited lower levels of both parenchymal and cerebrovascular HS. Additionally, ApoE4 carriers displayed heightened cerebrovascular Aβ expression and a tendency of elevated cerebrovascular HS levels in AD patients with severe CAA. Overall, these findings shed light on the intricate interplay between HS, Aβ, ApoE, and vascular pathology in AD, underscoring the potential roles of cerebrovascular HS in CAA development and AD pathology. Further exploring the underlying mechanisms may present novel therapeutic avenues for AD treatment.

Cardiovascular risk factors (CRFs) such as hypertension, high cholesterol, and diabetes are increasingly implicated in cognitive decline and cerebral small vessel disease (cSVD). White matter hyperintensities (WMH), a hallmark of cSVD, are strongly linked to cognitive impairment, but their underlying mechanisms remain unclear. Blood-brain barrier (BBB) dysfunction has been proposed as a potential contributor to WMH development. This study aimed to explore the relationships between CRFs, BBB integrity, and WMH burden. We analyzed 155 participants from the Biomarkers and Cognition Study, Singapore, assessing CRFs through blood tests for glucose and lipid profiles, alongside blood pressure measurements. WMH volume was quantified using MRI, and an in vitro assay evaluated the impact of plasma on BBB integrity using human brain microvascular endothelial cells. Results showed that plasma from participants with higher WMH burden correlated with increased BBB disruption, which was further associated with higher blood pressure, elevated blood glucose, and lipid levels. Both periventricular and subcortical WMH were linked to BBB disruption. These findings suggest that CRFs contribute to BBB dysfunction, promoting WMH development and cognitive decline in cSVD. Further research is needed to clarify the precise mechanisms driving these associations.

High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham=-7.499, LogIC50 Stroke=-7.350, P=0.0132, n= 19, 31 respectively). Vasodilatory responses to SNP were identical in isolated aortas in sham and stroke groups. Phenylephrine induced vasoconstriction was impaired in aortas isolated from stroke animals in comparison to sham counterparts (Sham LogEC50= -6.652 vs Stroke LogEC50=-6.475, P< 0.001). Our study demonstrates that 24 hours post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. Aortas from stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while endothelium-independent vasodilatory responses were preserved. Since both vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke.

Cerebral blood flow (CBF) decreases across the lifespan, and chronic conditions such as dementia and stroke accelerate this decline. Impaired CBF results in reduced delivery of oxygen and nutrients, which can damage the brain over time. Thus, there is a need to identify lifestyle interventions including diet and exercise to maintain CBF with aging and in the presence of chronic disease. In the present study, we used transcranial Doppler ultrasound to record middle cerebral artery velocity (MCAv), a surrogate measure of CBF, during moderate-intensity exercise in sedentary, cognitively-normal older adults (N = 90). A multiple linear regression model (F(4, 85) = 3.21, p = 0.02) showed self-reported omega-3 supplement use significantly moderated the association between age and mean exercising MCAv in these individuals (p = 0.01). Older age was associated with lower exercising MCAv in the group not taking omega-3 supplements, while exercising MCAv showed no decline with increasing age in the group who reported omega-3 supplement use. These findings suggest omega-3 supplementation may have an important role in the preservation of CBF with aging.

Cerebral Palsy (CP) poses substantial challenges to individuals, affecting their physical capabilities and daily functioning, and necessitates tailored interventions to enhance their quality of life and independence. Hand functionality is often affected in more than 60% of individuals with CP; they (mostly children) may spend up to 2-3 hours tightening their shoes perfectly. This includes the tightening of laces, standing up to determine if it is sufficient, and having to repeat the process many times till desired throughout the day. This paper focuses on the development of such a system that will assist them in effectively reducing this time to an approximate maximum time of 10 minutes. In its proposed form, this would reduce the shoe-tying process and make it ~18 times faster. The system will allow the user to perform the process with one hand and be simple and reliable. This additional freedom, among utilization of other systems, could lead to a betterment in mental health regarding the desire to perform outdoor activities among individuals with CP

Radiologists refer to any area of cerebral parenchymal loss with or without surrounding gliosis as encephalomalacia. This archaic phrase, which literally translates to "softening of the brain" due to liquefactive necrosis, was coined by pathologists to describe the macroscopic appearance of the brain following a variety of traumas, such as cerebral infarction. The final outcome of brain parenchymal liquefactive necrosis after insult, which typically happens after cerebral ischemia, cerebral infection, hemorrhage, traumatic brain damage, surgery, or other insults. Gliosis, or the growth of glial cells in reaction to injury, is frequently seen around it. The location, size, and number of the lesions as well as the existence of other issues like seizures, hydrocephalus, or infection affect the symptoms and prognosis of encephalomalacia. While some people might not have any symptoms, others might have neurological abnormalities such hemiparesis, aphasia, cognitive decline, or behavioral changes. Depending on the underlying reason and the severity of the problem, treatment options may include medication, surgery, or rehabilitation. This is a case of a young male who reported for rehabilitation his left upper limb weakness, upon investigations Encephalomalacia was diagnosed.

Infective endocarditis is a rare and challenging diagnosis, Q fever endocarditis being a major cause of culture-negative endocarditis (IE). The presence of multiple cerebral microbleeds (CMBs) suggests a particular vascular frailty and could be correlated to potential emergence of a haemorrhagic stroke in IE. We report a case of a 45 years-old patient with Coxiella burnetii endocarditis, with a brainstem hemorrhage and cerebral MRI CMBs resembling those of CAA. However the systemic inflammatory tests, the splenic infarct and kidney pathology could not be explained by a variant of CAA, neither the normal initial cerebral CT scan when the patient had already the brainstem clinical signs without evidencing the hemorrhage. Transthoracic and transesophageal echocardiogram revealed only calcified bicuspid aortic valve with moderate stenosis and regurgitation, without any vegetations and the blood cultures on conventional media were negative. Serology for Coxiella burnetii was positive. Inclusion of CMBs as a new minor imaging criteria for infective endocarditis could upgrade the diagnosis in almost 50% of patients.

Background: Formation and rupture of cerebral aneurysms may be related to certain types of configuration of the circle of Willis. Analysis of their interdependence can be of great importance. Methods: A group of 114 patients treated operatively for the cerebral aneurysm rupture and a group of 56 autopsied subjects were involved in the study. Four basic types of the circle of Willis configurations were formed–two symmetric types A and C, and two asymmetric types B and D. Results: A statistically significantly higher presence of asymmetry of the circle of Willis in the group of surgically treated subjects (p=0.006) with a significant presence of asymmetric Type B in this group (p=0.017) were determined. The presence of changes in the A1 segment in the group of subjects with solitary aneurysms on the anterior communicating artery showed a statistically significant presence in the group of autopsied subjects (p=0.0004). Analyzing the presence of symmetry of the circle of Willis between the two groups, that is, the total presence of symmetric types A and C indicated their statistically significant presence in the group of autopsied patients (p=0.043). Conclusion: Changes such as hypoplasia or aplasia of A1 and the resulting asymmetry of the circle of Willis directly affect the possibility of the rupture of cerebral aneurysms. Detection of the corresponding types of the circle of Willis after diagnostic examination can be the basis for the development of a protocol for monitoring such patients.

Introduction The monitoring of cerebral perfusion in patients with brain damage is a major clinical challenge. Monitoring cerebral oxygenation (rSO2) by NIRS was introduced at the turn of the 1980s, and many clinicians believed it was a valuable method for assessing cerebral perfusion and subsequent measures to optimize cerebral flow. The main problem of NIRS usage is the presence of the intermediate structures-skin, skull, meninges, cerebrospinal fluid-and their influence on the outcome of the test. Therefore, it seems that NIRS assessment performed on a patient during brain death attempts, can give an idea of the magnitude of the influence of these intermediate structures on the monitoring result. Case We present a retrospective analysis of cerebral oxygenation measurements of a patient undergoing a brain death diagnostic procedure. A clinical situation where the cerebral blood flow is stopped can give an idea of the specificity of the method, particularly the impact of the influence of intermediate structures on the monitoring outcome. In this case, the NIRS result is increased by the oxygenation of the patient before the apnoea test. The influence of chromophores in the tissues surrounding the CNS, reflections and scattering of the light wave spectrum have a very significant effect on the final result of cerebral saturation measurement. Discussion The majority of research observations describing changes in cerebral perfusion or its optimisation may be burdened by the problem described, i.e. the significant influence of measured oxygenation from intermediate structures. The specificity of NIRS to assess cerebral perfusion requires careful analysis. The therapeutic implications of monitoring cerebral oxygenation with NIRS are of great importance and, from the example presented and the literature provided, the method should be used with caution. It has been shown that in a patient with brain death, the result of NIRS oxygenation measurements depends on the surrounding structures of the brain.

Hematoma caused by rupture of a pseudoaneurysm in the middle meningeal artery (MMA) after trauma usually present with epidural hematoma. Intracerebral hemorrhage (ICH) is extremely rare. We reviewed ICH due to rupture of MMA pseudoaneurysm. We found that in cases of acute ICH, a pseudoaneurysm was attached to the outer surface of the dura mater and associated with dura tear. In patients with acute ICH, intraoperative rupture of pseudoaneurysm developed just after bone flap removal. In cases of delayed ICH, pseudoaneurysms adhered to the inner surface of the dura mater. In patients with delayed ICH, intraoperative rupture of pseudoaneurysm developed during dura opening and hematoma removal. In situations of dura tear after trauma, rupture of pseudoaneurysms might lead to ICH via a dura tear. Pseudoaneurysms that develop in the MMA after trauma may exert pressure on and result in the thinning of the dura mater. In this case, pseudoaneurysms will adhere to the inner surface of the dura mater after several days or weeks. ICH might develop through both acute and delayed mechanisms following development of pseudoaneurysms in the MMA. Clinicians should pay attention to the timing of such ruptures during operations for both acute and delayed ICH.

Abstract Cerebral microbleed(s) (CMBs) are increasingly being viewed not only as a marker for cerebral small vessel disease (SVD) but also as having an increased risk for the development of stroke (hemorrhagic/ischemic) and aging-related dementia. Recently, brain endothelial cell activation and dysfunction and blood-brain barrier dysfunction and/or disruption have been shown to be associated with SVD, enlarged perivascular spaces, and the development and evolution of CMBs. CMBs are a known disorder of cerebral microvessels that are visualized as 3-5mm, smooth, round or oval, and hypointense (black) lesions seen only on T2*-weighted gradient recall echo or susceptibility-weighted sequences on MRI images. CMBs (a global problem) are known to occur with high prevalence in community-dwelling older individuals. Since our current global population is the oldest recorded in history and only expected to continue to grow, we can only expect the health care burdens associated with CMBs to also grow. CMBs should raise a red flag regarding the increased risk of large symptomatic neurologic intracerebral hemorrhages. Importantly, CMBs are also currently regarded as markers of diffuse vascular and neurodegenerative brain damage. Thus, it is essential that we try to learn as much as we can about their development, evolution, and their relation to impaired cognition, dementia, and neurodegeneration.

(1) Background: Most patients with atrial fibrillation, on warfarin therapy, are at higher risk of morbidity and mortality. However, data targeting patients with atrial fibrillation, who take warfarin therapy, are limited in Jordan. This study aimed to provide in-depth analysis of a cohort of patients with atrial fibrillation on warfarin regarding patients’ characteristics, atrial fibrillation related symptoms, interventions, comorbidities, and 12-months outcomes. (2) Methods: The study enrolled 645 patients with atrial fibrillation, on warfarin, from 28 health settings across Jordan. Standardized clinical data form was utilized to collect data upon enrollment, at one, six, and 12 months post initial assessment. Descriptive statistics were used for the description of variables. (3) Results: The most commonly reported symptoms were palpitation (41.4%) shortness of breath (39.1%) and fatigue (26.2%). The prevalent comorbidities associated with atrial fibrillation were congestive heart failure (22.5%), valvular heart diseases (16.6%), and cerebral vascular accident (16.3%). The embolic (32.4%) and thrombotic cerebral vascular accident (16.2%) were the most common type. Major bleeding associated with hospitalization was the most frequent type of bleeding (10 out of 24). (4) Conclusions: Jordanians, using anticoagulation, need to be constantly monitored in terms of their characteristics, symptoms, and any potential complications, to ensure its optimal therapeutic dose and prevent any potential health complications.

A rare neurological condition known as Dyke-Davidoff-Masson syndrome (DDMS) is characterized by cerebral hemiatrophy, facial asymmetry, contralateral motor impairment, and seizures. Cerebral hypoplasia, ventriculomegaly, paranasal sinus hyper-pneumatization, and compensatory osseous expansion are classic imaging findings. The relationship between clinical and neuroimaging findings provides the basis for the diagnosis of DDMS. DDMS is treated with anticonvulsant medication and physical therapy. This is the case of a 26-year-old male, with a known case of cerebral palsy and on antiepileptics for 15 years, who presented with complaints of generalized weakness, vomiting, difficulty walking, recurrent convulsions, and a recent episode of generalized tonic-clonic seizures. Neuroimaging revealed findings significant of Dyke Davidoff Masson Syndrome. Understanding its imaging and clinical characteristics facilitates prompt and precise diagnosis, permitting appropriate management.

Cannabinoids are prescribed to children with cerebral palsy (CP) despite limited evidence. We aimed to assess the prescription practices of cannabinoids in children with CP with a particular focus on indications, what kind of preparations are used and how well cannabinoids are tolerated. Furthermore, we investigated how physicians acquire knowledge on cannabinoid medication. We asked physicians with expertise in the care of children with CP about their prescription prac-tices of cannabinoids. Data was collected through an online survey, which was distributed by email. In addition to the demographic information of participants, we also inquired about the indications for the prescription of cannabinoids, about experiences regarding efficacy, and ob-served side effects of the therapy. Seventy physicians from Europe, North America and Australia completed the survey. Forty-seven participants were experienced in the treatment of children with CP by cannabinoids. The most common indication was epilepsy (69%), followed by spasticity (64%) and pain (63%). The pre-scribed preparations and doses varied considerably. Half of the participants evaluated the effect of the cannabinoids as moderate. Twenty-nine physicians reported side effects, most frequently drowsiness (26%), somnolence (19%), fatigue (13%), and diarrhea (13%). Despite the lack of evidence to date, cannabinoids are used to treat children with CP in a wide variety of indications. Randomized controlled trials in this vulnerable patient group are therefore of utmost importance.

Introduction: Cerebral palsy is the most common childhood disability Aims: Analyze and determine the main risk factors for the development of cerebral palsy in the population of Kazakhstan Materials and methods: Retrospective, analytical "case" - "control". Core group "case" - medical records of 100 pregnant women whose children at different ages has been diagnosed with cere-bral palsy Results: Thus, a retrospective analysis revealed the following features and complications in the perinatal period, which could promote the formation of cerebral palsy in children. Analytical results of the study are set significant results in cerebral palsy development Conclusion: Premature birth and urinary tract infections turned out to be the largest contribu-tors to the development of cerebral palsy, however, according to statistics, the rate of preterm birth, as well as the detection of infections, stably remains at the same level, while the number of cerebral palsy has been steadily growing since the early 1990s in Kazakhstan.

Secondary and tertiary prevention strategies targeting people with disabilities to improve their health and wellbeing is important. In Sweden, >95% of all children with cerebral palsy (CP) participate in a follow-up program, where one of the goals is the prevention of hip dislocations. We reviewed the incidence of hip dislocations from 2010 to 2019 and the number of children who underwent different types of hip surgeries. The number of hip dislocations was reduced from 8.8% before introduction of the program to 0.3-0.4% up to 2015, followed by a gradual increase to 0.8% in 2019. The proportion of children who underwent adductor-psoas lengthening as their primary preventive surgery decreased from 50% in 2017 to 37% in 2019 with a corresponding increase of children undergoing femoral osteotomy, indicating more children underwent surgery at a later stage. Reasons for the increased number of children with hip dislocation may be that more children have moved to Sweden in recent years without corresponding compensation in health care resources and increased waiting times for surgery due to, among other things, a shortage of nurses. The results highlight the importance of constantly monitoring follow-up programs.

Aim: To develop an index for quantitative assessment of the upper limb motor function in children with cerebral palsy before and after robot-assisted therapy. Method: An upper limb motor function index was developed using kinematic, surface electromyography and three-axis inertial measurements unit data collected from 15 children with cerebral palsy (CP) and 15 typically developed children. Children with CP underwent 18 robot-assisted therapy sessions with the REAplan device. All children were evaluated, using kinematic data from the REAplan, electromyography and three-axis inertial measurements unit readings from its accelerometer. A principal component analysis was conducted to produce an evaluation index, which is able to detect the deviation from the upper limb motor function of typically developing children group. Children with CP were evaluated twice before and after the intervention with Box and Blocks test and Finger-To-Nose test. The discriminative and concurrent validity of the upper limb motor function index were investigated. Results: The upper limb motor function index was higher in children with CP post therapy (p<0.001). Finger-To-Nose test values improved after robot-assisted therapy (p<0.03). A weak but positive correlation was observed between upper limb motor function index and clinical tests (r=0.012, p=0.95 and r=0.13, p= 0.54 for Box and Blocks test and Finger-To-Nose test respectively). Interpretation: The upper limb motor function index successfully differentiated between the typically developing children and children with CP and was effective in assessing the improvement of the upper limb motor function after robot-assisted therapy. The upper limb motor function index could be extended to assess and monitor rehabilitation therapies of other populations, such as those with stroke and Parkinson’s disease.

A retrospective cohort study was performed to determine the likelihood of malignant stroke after mechanical thrombectomy via ASPECTS-PASS score(A-P score), a novel scoring system using ASPECT score and number of arterial-passes. This prediction score is designed to help clinicians take early measures. Malignant stroke is defined as a large MCA infarct with mass effect that develops during the first 5 days following presentation and is associated with approximately 80% mortality. Previous studies have shown an association of low ASPECTS and high number of passes with poor outcome.We performed a retrospective cohort analysis on 78 patients with anterior circulation stroke who underwent mechanical thrombectomy at our hospital. We analyzed the likelihood of developing malignant stroke post thrombectomy in the first 5 days following successful recanalization (TICI ≽ 2b). Malignant stroke is defined as severe symptoms secondary to edema as evidenced by midline shift, cistern engorgement, and hemorrhagic conversion with edema. Patients with ASPECTS of 0-5 were excluded. We used two variables to predict the outcome: ASPECT score and number-of-passes. We used the equation ASPECT score minus number-of-passes (A-P) to arrive at a single number to predict the risk of malignant stroke. A-P scoring scale ranged from 0-9. Our study showed a statistically significant inverse relationship of A-P score and risk of malignant stroke. Approximately 90% of patients with A-P score < 5 developed malignant stroke in our study. A-P score can help predict malignant stroke post thrombectomy even after successful recanalization. Thus, A-P score of ≤ 5 suggests very high risk. (A-P) Score can assist clinicians to take early measures, and thereby prevent worse outcomes.

Perinatal asphyxia is a leading cause of neonatal morbidity and mortality, often resulting in hypoxic-ischemic encephalopathy (HIE) with lasting neurodevelopmental impairments. Therapeutic hypothermia has been proposed as a treatment to mitigate brain damage, but its effects on specific brain structures remain under investigation. This study explores the relationship between cerebral volumetry, cortical thickness, and neurodevelopment in term neonates with perinatal asphyxia, with or without therapeutic hypothermia. A prospective cohort of term neonates with perinatal asphyxia was divided into two groups: one group exposed to therapeutic hypothermia and another group from a different institution that did not receive therapeutic hypothermia (non-exposed). Brain MRI data were analyzed using Infant-FreeSurfer and machine learning algorithms to quantify volumes of the basal ganglia, gray matter, white matter, cortical gyri, cerebellum, and cortical thickness. Neurodevelopment was assessed using the Bayley Scale III, focusing on motor, cognitive, and language domains, with additional genetic analyses of neurodevelopmental markers. Statistical comparisons adjusted for therapeutic hypothermia revealed significant differences in brain volumes. Hypothermia-treated infants demonstrated increased gray and white matter volumes and greater cortical thickness in specific regions, correlating with improved neurodevelopmental outcomes. These findings suggest that therapeutic hypothermia has a neuroprotective effect on specific brain structures, contributing to better cognitive and motor development. The study underscores the potential of therapeutic hypothermia as a critical intervention for perinatal asphyxia. It highlights the need for further research on its long-term benefits, incorporating advanced neuroimaging techniques and genetic insights to optimize outcomes.

Cerebral aneurysms come in a wide range of shapes and sizes, they can evolve over time and present significant changes. It is generally accepted that large aneurysms are more prone to rupture, but the rupture of small aneurysms has also been observed, indicating the presence of additional risks factors. The aim of this study is to assess the effects of the aneurysm size and wall thickness on its rupture risk by using fluid-structure interaction simulations. Six patient-specific geometries were chosen, four were used for studying the size effect and two for studying the thickness effect. Additional cases where the aneurysm was removed were included. It was found that thinner walls suffer from significantly greater stresses, whereas an increment in size means, in general, lower wall shear stress and greater equivalent stress. By removing the aneurysm, it could be noted that at the rupture point, the reduction in the time-averaged wall shear stress was 75%. Although the size of an aneurysm has a great impact in its rupture risk, its wall thickness needs to be considered, since even maintaining its size, the aneurysm could suffer from a thin-ning of its walls that can lead to structural failure.

Cerebral palsy (CP) presents challenges in movement and posture due to central nervous system damage, necessitating lifelong management. The COVID-19 pandemic has limited access to traditional treatments, increasing demand for home-based therapies and digital resources. This study analyzed the qualitative and quantitative aspects of YouTube videos focusing on CP therapy for children. In total, 95 videos were evaluated for content quality, therapeutic program efficacy, and popularity. Most videos were uploaded by health professionals. Neuromotor therapy types varied, with Bobath therapy being prominent. The quality assessments revealed moderate to high reliability in video content; nonetheless, shortcomings in addressing uncertainties were observed. Therapeutic programs often lack crucial details such as intensity and outcome assessment methods. No significant differences were found between professional and non-professional uploads. Classifiable videos based on exercise type, in contrast to the types of neuromotor therapy, exhibited better therapeutic quality than unclassified ones. Notably, video popularity did not correlate with quality. This study underscores the need for improved educational content on YouTube, particularly in providing comprehensive therapeutic information for CP management. Further refinement of evaluation tools is essential for assessing the rationale behind neuromotor therapeutic modalities for children with CP.

This paper deals with the analysis of the cognitive functions of the cerebral cortex or cortex in the evolutionary context. The triune brain model is presented given its notorious popularity in fields that are not strictly neuroscientific, and its limitations and inaccuracies are also shown. Although it is an outdated theory, this one represented the passage to a new era, because it really was the model of the movement towards understanding the brain in evolutionary terms. Next, the paper illustrates the different areas of the cortex and their functions, as well as the evolution of the brain and the cortex in vertebrates. To date, the expansion of the cortex with the amniotes was placed 300 million years ago, although recent studies place it in the lampreys more than 500 million years ago. Evolutionary changes in mammalian brain and cortex size are discussed, showing the evolution from three to six cell layers and trends in different groups of mammals. Finally, the most recent contributions in the field of research are illustrated, such as the role of neurogenesis and the evolution of the connectivity of the cortex.

The pathogenesis of Cerebral Small Vessel Disease (CSVD) is largely unknown. Endothelial disfunction has been suggested as the turning point in CSVD development. In this study we tested the effect of plasma from CSVD patients on human cerebral microvascular endothelial cells with the aim of describing the pattern of endothelial activation. Plasma samples from 3 groups of young subjects have been tested: PTs (subjects affected by early stage CSVD); CTRLs (control subjects without abnormalities at MRI scanning); BDs (blood donors). Human Brain Endothelial Cells 5i (HBEC5i) were treated with plasma and total RNA was extracted. RNAs were pooled to reduce gene expression-based variability and NGS analysis was performed. Differentially expressed genes were highlighted comparing PTs, CTRLs and BDs with HBEC5i untreated cells. No significantly altered pathway was evaluated in BD related treatment. Regulation of p38 MAPK cascade (GO:1900744) was the solely pathway altered in CTRLs related treatment. Indeed, 36 different biological processes turned out to be deregulated after PTs treatment of HBEC5i, i.e., the cytokine-mediated signaling pathway (GO:0019221). Endothelial cells activate inflammatory pathways in response to stimuli from CSVD patients’ plasma, suggesting the pathogenetic role of neuroinflammation from the early asymptomatic phases of cerebrovascular disease.

The COVID-19 pandemic has caused unprecedented challenges in the care of children with cerebral palsy (CP) and other neuromuscular complex chronic conditions (NCCC). The purpose of this study was to explore the direct impact of the COVID-19 pandemic on healthcare delivery. From May to August 2020, medical professionals caring for CP and NCCC patients across multiple countries and disciplines completed a self-administered cross-sectional survey comparing practices before and during the COVID-19 pandemic. Of the 79 healthcare workers from 8 countries who participated—predominantly pediatric orthopedic surgeons (32%), pediatricians (30%), and pediatric physiatrists (23%)—most felt that caring for NCCC patients during the pandemic presented with unique difficulties and reported a significant decrease in in-person NCCC clinic volume (p<0.001), multidisciplinary appointments (p<0.001), surgical cases (p=0.005), and botulinum toxin/phenol injections. Most providers affirmed that institutional guidelines for perioperative emergent/urgent and elective procedures, workplace settings, and technology were modified to accommodate the ongoing public health crisis. Usage of telemedicine significantly increased for NCCC patient visits (p<0.001). During the COVID-19 pandemic, many children with NCCC lost access to routine, multidisciplinary care. Telemedicine became an integral part of communication and management. In the setting of the COVID-19 pandemic and threat of future healthcare disruptions, these data lay the foundation for trending the evolution of healthcare delivery and accelerating best practice guidelines for children with CP and NCCC.

Doppler findings of persistent reverse end-diastolic flow (PREDF) in a fetal middle cerebral artery (MCA) are a very rare sonographic finding and are a marker of poor fetal condition. This finding often leads to intrauterine fetal death or early neonatal death. The reverse end-diastolic flow in the middle cerebral artery is the terminal hemodynamic event. Fetal cerebral circulation normally has a high impedance; in the event of fetal hypoxemia, impedance decreases, resulting in the central redistribution of blood flow to vital organs, which maintains the oxygen delivery to the brain. Reverse flow in the middle cerebral arteries describes the loss of this autoregulatory process. PREDF is a sequence happening due to increased extracranial or intracranial pressure. Previous case reports mentioned intracranial hemorrhage, intrauterine growth restriction (IUGR), fetal anemia, and fetal hepatic abnormalities as leading problems to PREDF. This condition presumably arises due to cerebral edema associated with severe hypoxemia. We reported Doppler findings of PREDF MCA in a 33-year-old female at 30 weeks gestation who was referred to the hospital with severe preeclampsia accompanied by IUGR and oligohydramnios. A cesarean section was performed due to severe preeclampsia and a low bishop score. Hypotheses on various etiologies and their association with intrauterine/neonatal death as well as the best management still require further investigation.

About 70% of children and adolescents with cerebral palsy experience gait impairments which affect their autonomy and well-being. Robotic-assisted gait training using the Lokomat is particu-larly promising for rehabilitation as it provides a standardized environment favoring the massive repetition of the movement, in which physical demands are low on the therapist and high training loads can be achieved. As no guidelines exist regarding training protocols and Lokomat settings, the goal of this study was to review the literature on Lokomat-assisted gait therapy and possibly make training recommendations. The twelve studies reviewed reported both positive and null effects of Lokomat training on gait. Half of the studies combined Lokomat with other types of training and only five used a control intervention to assess its benefit. Overall, training was administered 1-5 times per week for 20-60 minutes, over 1-12 weeks. Although Lokomat settings were not always described, progressively decreasing body-weight support and guidance, while increasing treadmill speed appear to be prioritized. The variety of training protocols and settings used did not allow pooling of the studies to assess effects of interventions on gait parameters in children and adoles-cents with cerebral palsy. This review highlights the need for homogenization of interventions so that clear guidelines can emerge and be applied in rehabilitation centers.

The authors propose a novel approach for a comprehensive evaluation of neuroprotective effects using both in vitro and in vivo methods. This approach allows for the initial screening of numerous newly synthesized chemical compounds and substances from plant and animal sources while preserving animal life. In vitro techniques, including mitochondrial suspensions and neuronal cell cultures, enable assessment of neuroprotective activity, which can be challenging in intact organisms. The preliminary methods help outline the neuroprotection mechanism depending on the neurodestruction agent. The authors have validated a model of acute cerebrovascular accident, which simulates key cerebrovascular phenomena such as reduced cerebral blood flow, energy deficit, glutamate-calcium excitotoxicity, oxidative stress, and early gene expression. A significant advantage of this model is its ability to reproduce the clinical picture of cerebral ischemia: impaired motor activity, signs of neurological deficits (paresis, paralysis, etc.), as well as disturbances in attention, learning, and memory. Crucial to this approach is the selection of biochemical, molecular, and cellular markers to evaluate nerve tissue damage and characterize potential neuroprotective agents. Additionally, a comprehensive set of molecular, biochemical, histological, and immunohistochemical methods is proposed for evaluating neuroprotective effects and underlying mechanisms of potential pharmaceutical compounds.

This study explores the potential of using a Siamese Network as a biomarker for assessing the effectiveness of Dolphin-Assisted Therapy (DAT) in children with Cerebral Palsy (CP). The problem statement revolves around the need for objective measures to evaluate the impact of DAT on patients with CP, considering the subjective nature of traditional assessment methods. The methodology involves training a Siamese network, a type of neural network designed to compare similarities between inputs, using data collected from CP patients undergoing DAT sessions. The network is trained to learn patterns and similarities between pre- and post-therapy evaluations, in order to identify biomarkers indicative of therapy effectiveness. Notably, the Siamese Network’s architecture ensures that comparisons are made within the same feature space, allowing for more accurate assessments. The results of the study demonstrate promising findings, indicating different patterns in the output of the Siamese Network that correlate with improvements in symptoms of CP post-DAT. These findings suggest the potential utility of the Siamese Network as a biomarker to monitor therapy outcomes in children with CP who undergo DAT, offering a more objective and quantifiable approach to assessing therapeutic interventions. Significant disparities in neuronal voltage perturbations, with a mean of 7.9825 dB in specific samples compared to 6.2838 dB in the data set, indicate a marked difference from resting activity. This suggests that dolphin-assisted therapy selectively activates specific brain regions uniquely during the intervention.

Recanalization poses challenge in coil embolization for cerebral aneurysms. Establishing predictive models for post-embolization recanalization is important for clinical decision-making. However, conventional statistical and machine learning (ML) models may overlook critical parameters during the initial selection process. In this study, we automated the identification of significant hemodynamic parameters using a PointNet-based deep neural network (DNN), leveraging their inherent 3D features. Further feature analysis was conducted utilizing saliency mapping, an explainable artificial intelligence (XAI) technique. The study encompassed the analysis of velocity, pressure, and wall shear stress (WSS) in both pre- and post-coiling models derived from computational fluid dynamic (CFD) simulations for 59 aneurysms. Velocity was identified as the most pivotal parameter, supported by the lowest P-value from statistical analysis and the highest area under the curves (AUROC)/precision-recall curves (AUPRC) values from DNN model. Moreover, visual XAI analysis revealed robust injection flow zones with notable impingement points in pre-coiling models, as well as pronounced interplay between flow dynamics and the coiling plane were important 3D features in identifying the recanalized aneurysms. The combination of DNN and XAI was found to be an accurate and explainable approach not only at predicting post-embolization recanalization but also at discovering unknown features in the future.

Cerebral palsy (CP) is the most common movement disorder in children with a prevalence rang-ing from 1.5 to 4 per 1000 live births. CP is caused by a non-progressive lesion of the developing brain, leading to progressive alterations of the musculoskeletal system, including spasticity, often leading to the development of fixed contractures, necessitating tendon lengthening surgery. Total RNA-sequencing analysis was performed on semitendinosus tendons from diplegic and tetraple-gic CP patients subjected to tendon lengthening surgery compared to control patients undergoing anterior cruciate ligament reconstructive surgery. Tetraplegic CP patients showed increased ex-pression of genes implicated in collagen synthesis and extracellular matrix (ECM) turnover, while only minor changes were observed in diplegic CP patients. In addition, tendons from tetra-plegic CP patients showed an enrichment for upregulated genes involved in vesicle-mediated transport and downregulated genes involved in cytokine and apoptotic signaling. Overall, our results indicate increased ECM turnover with increased net synthesis of collagen in tetraplegic CP patients without activation of inflammatory and apoptotic pathways similar to observations in athletes where ECM remodeling results in increased tendon stiffness and tensile strength. Never-theless, the resulting increased tendon stiffness is an important issue in clinical practice, where surgery is often required to restore joint mobility.

Horse riding therapy, also known as hippotherapy, is a popular treatment for children with cerebral palsy (CP). However, the need for trained therapists, massive land use, and expensive maintenance of the horse ranch makes hippotherapy not affordable or even available for most patients in Indonesia. This problem motivates us to consider mechanical horse riding simulator machines to replace actual horse hippotherapy. However, most patients are children and are easily bored when asked to do monotonous activities for an extended period. The room setting also does not give the patient visual inputs that usually help motivates the children in real-horse hippotherapy activities. To solve this problem, we designed an exercise game (exergaming) software which we named \textit{Sirkus Apel}, providing the patients with fun activities while doing the therapy. We also design an inertial sensor-based controller that lets the patients control the in-game horse by their back movements, which also benefits CP patients. To make the visual input enjoyable to the user while also considering the user's safety, we built a convex mirror-based dome virtual reality to provide an immersive 3-D experience. We then project the game content to the dome to provide an immersive experience to the patients making it as if they are riding a real horse inside the game.

Objectives: Cerebral edema, a prevalent consequence of brain injury, is associated with significant mortality and disability. Timely diagnosis and monitoring are crucial for patient prognosis. There is a pressing clinical demand for a real-time, non-invasive cerebral edema monitoring method. Ultrasound methods are prime candidates for such investigations due to their non-invasiveness nature; Methods: Acute cerebral edema by permanently occluding the left middle cerebral artery (MCA) was introduced in rats. Ultrasonic echo signals were collected at nine time points over a 24-hour period to extract features from both the time and frequency domains. Concurrently, histomorphological changes were examined. We utilized support vector machine (SVM), logistic regression (LR), decision tree (DT), and random forest (RF) algorithms for classifying cerebral edema types, and SVM, RF, and feedforward neural network (FNN) for predicting the cerebral infarction volume ratio; Results: The integration of 16 ultrasonic features associated with cerebral edema development with the RF model enabled effective classification of cerebral edema types with a high accuracy rate of 97.9%. Additionally, it provided an accurate prediction of the cerebral infarction volume ratio, with an R2 value of 0.8814; Conclusions: Our proposed strategy classifies cerebral edema and predicts the cerebral infarction volume ratio with satisfactory precision. The fusion of ultrasound echo features with machine learning presents a promising non-invasive approach for the monitoring of cerebral edema.

The aim of this study is to assess of rare earth elements (REE) content in hair samples in children, living in Lovozero village, near REE mining site, and possible effects of REEs on the prevalence of nervous system diseases in the Lovozersky district (Murmansk region, Kola Peninsula). School-age children (53 persons) were recruited for analysis of REE content in their hair samples. REEs (Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) content was estimated by inductively coupled plasma mass spectrometry (ICP-MS). Analysis of REE content in the hair of children living in the Russia, Kazakhstan and China indicates REEs intake from environment. A possible contribution of REEs to the nervous system disorders is supported by the link between REE content in the hair samples of children, living near REE mining (China) and by manifesting cognitive disorders in these children. It also turn out that highest prevalence of the nervous system diseases in children 15-17 years old manifested in the Lovozersky district then in other area in the Murmansk region. The paper discusses the possible contribution of REEs to the prevalence of episodic paroxysmal disorders (G40-G47), cerebral palsy (G80-G83), epilepsy and status epilepticus (G40-G41).

This study evaluates the R3THA™ technology-supported assessment protocol for home-based rehabilitation in children with cerebral palsy (CP). It focuses on the reliability and validity of R3THA™ in assessing hand and arm function, comparing kinematic assessments with standard clinical assessments. Conducted during a 4-week summer camp, the study involved children with CP aged 3-18, assessing their functional and impairment levels. The findings suggest that R3THA™ is more reliable for children aged 8 and older, indicating that age significantly influences the protocol's effectiveness. Results also showed that R3THA-AP's kinematic measurements of hand and wrist movements were positively correlated with the Box and Blocks Test Index (BBTI), reflecting hand function and dexterity. Additionally, R3THA-AP's accuracy metrics for hand and wrist activities aligned with the Melbourne Assessment 2's Range of Motion (MA2-ROM) scores, suggesting a meaningful relationship between R3THA-AP data and clinical assessments of motor skills. However, no significant correlations were observed between R3THA-AP and MA2's accuracy and dexterity measures, indicating areas for further research. These findings validate R3THA-AP's utility in assessing motor abilities in CP, supporting its integration into clinical practice.

Cerebral cavernous malformation (CCM) is a collection of irregular small blood vessels that may be present in the brain or spinal cord. These vessels contain slow – moving blood that commonly clot. These malformations are frequently caused by mutations in one of the CCM genes. The CCM1 (also known as KRIT1) gene is essential for vascular morphogenesis however, its interactions with transcriptional regulators are unknown. Inhibitor of DNA-Binding/Differentiation-3 (ID3) has been recognized to be involved in different vascular/blood vessel diseases such as peripheral arterial disease, stroke, arteriovenous malformations, and atherosclerosis. We show interactions between ID3 and additional key differential expressed genes (DEGs) in microarray data of overexpressed CCM1 in endothelial cells through bioinformatic and data analytic tools. Improved understanding of how ID3, CCM1, and DEGs interact will play an important role in adding to the increasing knowledge for creating therapeutic targets for cerebral cavernous malformations.

Angiostrongylus cantonensis, a zoonotic parasite, can invade the human central nervous system (CNS) and cause acute eosinophilic meningitis or eosinophilic meningoencephalitis. Mice infected with A. cantonensis show elevated levels of pro-inflammatory cytokines, plasminogen activators, and matrix metalloproteinase-9, resulting in disruption of the blood-brain barrier (BBB) and immune cell infiltration into the CNS. Caveolin-1 (Cav-1) regulates the permeability of the BBB, which affects immune cells and cerebrospinal fluid. This intricate interaction ultimately fuels the progression of brain damage and edema. This study aims to investigate the regulatory role of Cav-1 in the pathogenesis of meningoencephalitis induced by A. cantonensis infection. We investigate pathological alterations by triphenyl-tetrazolium chloride, brain water content, BBB permeability, Western blot analysis, and gelatin zymography in BALB/c mice after A. cantonensis. The study evaluates the critical role of Cav-1 regulation through the TLR4 / MyD88 signaling pathway, modulates tight junction proteins, influences BBB permeability, and contributes to brain damage in A. cantonensis-induced meningoencephalitis.

Background: Although cerebral aneurysm (CA) is a defining complication of COL4A1/2-related vasculopathy, the specific factors influencing its onset remain uncertain. This study aimed to identify and analyze these factors. Methods: We described a family presenting with a novel variant in the COL4A1 gene complicated with CA. Concurrently, an exhaustive review of previously documented patients with COL4A1/2-related vasculopathy was conducted by sourcing data from PubMed, Web of Science, Google Scholar, and Ichushi databases. We compared the variant types and locations between patients with CA (positive group) and those without CA (negative group). Results: This investigation encompassed 53 COL4A1/2 variants in 76 patients. Except for one start codon variant, all the identified variants in CA were missense variants. Otherwise, CA was not associated with other clinical manifestations, such as small-vessel disease or other large-vessel abnormalities. A higher frequency of missense variants (95.5% vs 58.1%, p = 0.0035) was identified in the CA positive group. Conclusions: CA development appears to necessitate qualitative alterations in COL4A1/2, and the underlying mechanism seems independent of small vessel disease or other large vessel anomalies. Our findings suggest that a meticulous evaluation of CA is necessary when missense variants in COL4A1/2 are identified.

Cerebral ischemia, which is a leading cause of disability and mortality worldwide, sets off a chain of molecular and cellular pathologies that are associated with some central nervous system (CNS) disorders, mainly including ischemic stroke, Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy and other CNS diseases. In recent times, despite significant advancements in the treatment of the pathological processes underlying various neurological illnesses, effective therapeutic approaches specifically targeted at minimizing the damage of such diseases remain absent. Remarkably, ischemia causes severe damage to cells in Ischemia-associated CNS Diseases. Cerebral ischemia initiates oxygen and glucose deprivation, which subsequently promotes mitochondrial dysfunction, including MPTP opening, mitophagy dysfunction, and excessive mitochondrial fission, triggering various forms of cell death, such as autophagy, apoptosis, as well as ferroptosis. Ferroptosis, a novel type of regulated cell death (RCD), is characterized by iron-dependent accumulation of lethal reactive oxygen species and lipid peroxidation. Mitochondrial dysfunction and ferroptosis both play critical roles in the pathogenic progression of Ischemia-associated CNS Diseases. In recent years, growing evidence has indicated that mitochondrial dysfunction interplays with ferroptosis to aggravate cerebral ischemia injury. However, the potential connections between mitochondrial dysfunction and ferroptosis in Cerebral Ischemia have not yet been clarified. Thus, we analyze the underlying mechanism between mitochondrial dysfunction and ferroptosis in Ischemia-associated CNS Diseases. We also discovered that GSH depletion and GPX4 inactivation cause lipoxygenase activation and calcium influx following cerebral ischemia injury, resulting in MPTP opening and mitochondrial dysfunction. Additionally, dysfunction in mitochondrial electron transport and an imbalanced fusion-to-fission ratio can lead to the accumulation of reactive oxygen species and iron overload, which further contribute to the occurrence of ferroptosis. This creates a vicious cycle that continuously worsens cerebral ischemia injury. In this study, our focus is on exploring the interplay between mitochondrial dysfunction and ferroptosis, which may offer new insights into potential therapeutic approaches for the treatment of Ischemia-associated CNS Diseases.

The basilar arterial endothelium mediates blood-vessel relaxation, partly through release of nitric oxide (NO). Apoptosis of cerebrovascular endothelial cells is linked to high mortality rate in chickens infected with highly pathogenic avian influenza virus, but interestingly ducks exhibit greater resistance to this virus. In this study, we examined the responsiveness of duck basilar arteries (BAs) to various vasoactive substances, including 5-hydroxytryptamine (5-HT), histamine (His), angiotensin (Ang) II, noradrenaline (NA), acetylcholine (ACh), and avian bradykinin ornithokinin (OK), aiming to characterize the receptor subtypes involved and the role of endothelial NO in vitro. Our findings suggest that arterial contraction is mediated by 5-HT1 and H1 receptors, while relaxation is induced by β3-adrenergic and M3 receptors. Additionally, OK elicited a biphasic response in duck BAs, and Ang II had no effect. Endothelial NO appears to be crucial in relaxation mediated by M3 and OK receptors, but not β3-adrenergic receptors, in the duck BA. The reduced endothelial NO involvement in the receptor-mediated relaxation response in duck BAs represents a clear difference from the corresponding response reported in chicken BAs. This physiological difference may explain differences in lethality between ducks and chickens when vascular endothelial cells are infected by the virus.

Background: Intradialytic hypotension (IDH) is a critical pathological condition associated with all−cause mortality in patients undergoing hemodialysis (HD). However, few studies have investigated IDH-related changes in hepatic and cerebral regional tissue oxygen saturation (rSO2). This study investigated IDH-induced changes in hepatic and cerebral rSO2. Methods: Hepatic and cerebral rSO2 during HD were measured using an INVOS 5100C oxygen saturation monitor, and their percentage (%) changes during IDH development were analyzed. Ninety-one patients undergoing HD were investigated, including 20 with IDH development. Results: In patients with IDH, % changes in hepatic and cerebral rSO2 decreased at IDH onset. Additionally, the % change in hepatic rSO2 was significantly larger than those in cerebral rSO2 (P < 0.001). In patients without IDH, no significant differences were found between the % changes in hepatic and cerebral rSO2 at time of the lowest systolic blood pressure during HD. Multivariable linear regression analysis showed that the difference between the % change in cerebral and hepatic rSO2 was significantly associated with IDH development (P < 0.001) and ultrafiltration rate (P = 0.010). Conclusion: Hepatic and cerebral rSO2 significantly decreased in IDH development and hepatic rSO2 was more largely decreased than cerebral rSO2 at IDH onset.

The relationship between Parkinson's disease (PD), the second most common neurodegenerative disease after Alzheimer's disease, and palmitoylation, a post-translational lipid modification, is not well understood. In this study, we have analyzed the differential palmitome present in the cerebral cortex of PD patients compared to controls (n=4 per group) to better understand the role of protein palmitoylation in PD and the pathways altered in this disease. Data-mining of the cortical palmitome from PD patients and controls has allowed to: i) detect a set of 150 proteins with altered palmitoylation in PD subjects in comparison with controls, ii) describe the biological pathways and targets predicted to be altered by these palmitoylation changes, and iii) depict the overlap between the differential palmitome identified in our study with protein interactomes of the PD-linked proteins α-synuclein, LRRK2, DJ-1, PINK1, GBA and UCHL1. In summary, we have partially characterized the altered palmitome in the cortex of PD patients which is predicted to impact cytoskeleton, mitochondrial and fibrinogen functions, as well as cell survival. Our study points out that protein palmitoylation could have a role in the pathophysiology of PD, and that comprehensive palmitoyl-proteomics offers a powerful approach for elucidating novel cellular pathways modulated in this neurodegenerative disease.

Background: Plasma metabolites are associated with cognitive and physical function in the elderly. Because cerebral small vessel disease (SVD) and neurodegeneration are common causes of cognitive and physical function decline, the primary objective of this study was to investigate the associations of six plasma metabolites (two plasma phosphatidylcholines [PCs]: PC aa C36:5 and PC aa 36:6 and four sphingomyelins [SMs]: SM C26:0, SM [OH] C22:1, SM [OH] C22:2, SM [OH] C24:1) with magnetic resonance imaging (MRI) features of cerebral SVD and neurodegeneration in older adults. Methods: This study included 238 older adults in the Atherosclerosis Risk in Communities study at the fifth exam. Multiple linear regression was used to assess the association of each metabolite (log-transformed) in separate models with MRI measures except lacunar infarcts, for which binary logistic regression was used. Results: Higher concentrations of plasma PC aa C36:5 had adverse associations with MRI features of cerebral SVD (odds ratio of 1.69 [95% confidence interval: 1.01, 2.83] with lacunar infarct, and beta of 0.16 log [cm³] [0.02, 0.30] with log [White Matter Hyperintensities (WMH) volume]) while higher concentrations of 3 plasma SM (OH)s were associated with higher total brain volume (beta of 12.0 cm³ [5.5, 18.6], 11.8 cm³ [5.0, 18.6], and 7.3 cm³ [1.2, 13.5] for SM [OH] C22:1, SM [OH] C22:2, and SM [OH] C24:1, respectively). Conclusions: This study identified associations between certain plasma metabolites and brain MRI measures of SVD and neurodegeneration in older adults, particularly higher SM (OH) concentrations with higher total brain volume.

Introduction: This population-based retrospective cohort study assesses rates of adverse events (AEs) involving cerebral thromboembolism (CTE) after COVID-19 vaccines. Methods: Data were collected from the U.S. Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) Vaccine Adverse Event Reporting System (VAERS) database from January 1, 1990 to December 31, 2023. CTE AEs after COVID-19 vaccines were compared to those after influenza vaccines and after all other vaccines using proportional reporting ratio (PRR) analysis by time. Results: There are 5137 cerebral thromboembolism AEs reported in the 3 years (36 months) after COVID-19 vaccines compared to 52 AEs for the influenza vaccines over the past 34 years (408 months) and 282 AEs for all other vaccines (excluding COVID-19) over the past 34 years (408 months). The PRR’s are significant when comparing AEs by time from COVID-19 vaccines to that of the influenza vaccines (p < 0.0001) or to that of all other vaccines (p < 0.0001). The CTE AEs PRR by time (95% confidence intervals) for the COVID-19 vaccine AEs vs influenza AEs is 1120 (95% confidence interval (723-1730), p < 0.0001) and for COVID-19 vaccines vs all others is 207 (95% confidence interval (144-296), p < 0.0001). Cerebral venous thromboembolism AEs are female predominant with a female/male odds ratio of 1.63 (95% confidence interval (1.52-1.74), p < 0.0001). Conversely, cerebral arterial thromboembolism has a nonsignificant male preponderance. Cerebral venous thromboembolism is far more common than cerebral arterial thromboembolism over 36 months with an odds ratio (OR) of 14.8 (95% confidence interval 14.0-15.5, p < 0.0001). Atrial fibrillation, the most common identifiable cause of cerebral arterial thromboembolism, occurs far more commonly after the COVID-19 as compared to all other vaccines with a PRR of 123 (95% CI 88.3-172, p < 0.0001) Conclusions: There is an alarming breach in the safety signal threshold concerning cerebral thrombosis AEs after COVID-19 vaccines compared to that of the influenza vaccines and even when compared to that of all other vaccines. An immediate global moratorium on the use of COVID-19 vaccines is necessary with an absolute contraindication in women of reproductive age.

Early detection of neurological conditions is critical for timely diagnosis and treatment. Identifying cellular-level changes is essential for implementing therapeutic interventions prior to symptomatic disease onset. However, monitoring brain tissue directly through biopsies is invasive and high-risk. Bodily fluids such as blood or cerebrospinal fluid contain information in many forms, including proteins and nucleic acids. Particularly, cell-free DNA (cfDNA) has potential as a versatile neurological biomarker. Yet, our knowledge of cfDNA released by brain tissue and how cfDNA changes in response to deleterious events within the brain is incomplete. Mapping changes in cfDNA to specific cellular events is difficult in vivo, where many tissues contribute to circulating cfDNA. Organoids are tractable systems for examining specific changes consistently in a human background. However, few studies have investigated cfDNA released from organoids. Here, we examined cfDNA isolated from cerebral organoids. We found that cerebral organoids release quantities of cfDNA sufficient for downstream analysis with droplet-digital PCR and whole-genome sequencing. Further, gene ontology analysis of genes aligning with sequenced cfDNA fragments revealed association with terms related to neurodevelopment and autism spectrum disorder. We conclude that cerebral organoids hold promise as tools for the discovery of cfDNA biomarkers related to neurodevelopmental and neurological disorders.

Studies in the field of experimental hypnosis highlighted the role of hypnotizability in the physiological variability of the general population. It is associated, in fact, with a few differences which are observable in the ordinary state of consciousness and in the absence of suggestions. The aim of the present scoping review is summarizing them, and indicate their relevance to the neural mechanisms of hypnosis and to the prognosis and treatment of a few medical conditions. Individuals with high, medium and low hypnotizability scores display different cerebral functional differences – i.e., functional equivalence between imagery and perception/action, excitability of the motor cortex, interoceptive accuracy - possibly related to brain structural and functional characteristics -, and different control of blood supply at peripheral and cerebral level, likely due to different availability of endothelial nitric oxide. These differences are reviewed to support the idea of their participation in hypnotic behaviour and to indicate their prognostic and therapeutic usefulness in a few medical conditions.

Alzheimer’s disease (AD) is the most common form of neurodegenerative disease worldwide. A large body of work implicates insulin resistance in the development and progression of AD such that AD may be a form of brain insulin resistance. Moreover, impairment in mitochondrial function, a common symptom of insulin resistance, now represents a fundamental aspect of AD pathobiology. Ceramides are a class of bioactive sphingolipids that have been hypothesized to drive insulin resistance. Here we describe preliminary work that tests the hypothesis that hyperinsulinemia pathologically alters cerebral mitochondrial function in AD mice via accrual of the ceramides. Homozygous male and female ApoE4 mice were given chronic injections of PBS (control), insulin, myriocin (an inhibitor of ceramide biosynthesis), or insulin and myriocin over four weeks. Cerebral ceramide content was assessed using liquid chromatography-mass spectrometry. Mitochondrial oxygen consumption rates were measured with high-resolution respirometry, and H2O2 emissions were quantified via biochemical assays on brain tissue from the cerebral cortex. Significant increases in brain ceramides and impairments in brain oxygen consumption were observed in the insulin-treated group. These hyperinsulinemia-induced impairments in mitochondrial function were reversed with the administration of myriocin. Altogether, these data demonstrate a causative role for insulin in promoting brain ceramide accrual and subsequent mitochondrial impairments that may be involved in AD expression and progression.

Coptisine (Cop) exerts a neuroprotective effect in central nervous system disease, particularly ischemic stroke. However, its protective mechanism is still unclear. This study aimed to investigate the protective effect of Cop on cerebral ischemia-reperfusion (IR) rats with a middle cerebral artery occlusion model by integrating a gas chromatography-mass spectrometry (GC-MS) based metabolomics approach with biochemical assessment. Our results showed that Cop could improve neurobehavioral function and decrease the ischemia size in IR rats. In addition, Cop was found to decrease inflammatory mediators (e.g., prostaglandin D2 (PGD2) and tumor necrosis factor-α (TNF-α) and attenuate oxidative stress response (e.g., increase the superoxide dismutase (SOD) expression and decrease 8-iso-PGF2α level). Furthermore, GC-MS based cerebrospinal fluid (CSF) metabolomics analysis indicated that Cop influenced the level of glycine, 2,3,4-trihydroxybutyric acid, oleic acid, glycerol, and ribose during IR injury. Cop exhibited a good neuroprotective effect against cerebral IR injury and metabolic alterations which might be mediated through its antioxidant and anti-inflammatory property.

The third trimester of pregnancy is the most critical period for human brain development, during which significant changes occur in the morphology of the brain. The development of sulci and gyri allows considerable increase of the brain surface. In premature childrens, these alterations take place outside the womb that may cause a disruption of the normal brain maturation process. We hypothesize that a normalized atlas of brain maturation with cerebral ultrasound images from birth to term equivalent age will help clinicians assess these changes. This work proposes a semi-automatic GUI platform for segmenting the main cerebral sulci in the clinical setting from ultrasound images. This platform has been obtained from images of a cerebral ultrasound neonatal database images provided by two clinical researchers from the Hospital Sant Joan de Déu in Barcelona, Spain. The primary objective is to provide a user-friendly design platform for clinicians, for running and visualizing an atlas of images validated by medical experts. This GUI offers different segmentation approaches, pre-processing tools, and is friendly designed for running, visualizing images, and segmenting the principal sulci. The presented results are discussed in detail in this paper, providing an exhaustive analysis of the proposed approach’s effectiveness.

Introduction: CT perfusion (CTP) is an alternative tool to assess cerebral hemodynamics in brain trauma. As traumatic acute subdural hematomas (ASH) are severe lesions commonly associated with poor outcome, we aimed to evaluate the brain hemodynamics in this population. Methods: Five patients admitted at the emergency department sustaining traumatic acute subdural hematoma were evaluated. Preoperative CTP was performed immediately after nonenhanced head CT scan. Postoperative CTP was performed in four patients. The outcome was assessed 6 months after surgery using the extended Glasgow Outcome Scale. Results: 4 male and 1 female were evaluated. Mean age was 46y (SD: 8.1). Mean preoperative midline brain shift was 10.1 mm (SD: 1.8). The main mechanism of trauma was falling (four patients). There was a general improvement in cerebral blood flow (CBF) after surgery from 23.9 (SD: 6.1) to 30.7 ml/100g/min, (SD: 5.1) and in mean transit time (MTT) from 7.3 (SD: 1.3) to 5.8s (SD:1.0), although it is not statistically significant (p=0.06 and p=0.06, respectively). There was still a reduction in the cerebral blood volume (CBV) media when compared to the value after surgery, from 2.63 (SD: 1.10) to 2.34 ml/100g (SD: 0.67), which is not statistically significant (p=0.31). Spearman correlation test of postoperative and preoperative CBF ratio with outcome was 0.94 (p=0.054). Only one patient died (three days after surgery). This patient was victim of car crash and had the highest preoperative MTT (9.97 seconds) and CBV (4.51 ml/100 g). Conclusion: Post-operative improvement of hemodynamic CTP parameters may be correlated with outcomes after ASH. Further studies with larger samples are required to confirm this hypothesis.

Only cross-sectional studies have demonstrated muscle deficits in children with spastic cerebral palsy (SCP). The impact of functional impairments on altered muscle growth remains unclear. This prospective longitudinal study modelled the morphological muscle growth in 87 children with SCP (age range 6 months to 11 years, Gross Motor Function Classification System [GMFCS] level I/II/III=47/22/18). Repeated ultrasound assessments were performed during 2-year (y) follow-up with an interval of minimal 6 months. Three-dimensional freehand ultrasound was applied to assess medial gastrocnemius muscle volume (MV), mid-belly cross-sectional area (CSA) and muscle belly length (ML). Non-linear mixed models compared trajectories of (normalized) muscle growth between GMFCS-I versus GMFCS-II&amp;III. MV and CSA growth trajectories showed piecewise model with 2 breakpoints, with the highest growth before 2y and negative growth rates after 6-9y. Before 2y, children with GMFCS-II&amp;III already showed lower growth rates compared to GMFCS-I. From 2-9y, the growth rates did not differ between GMFCS-levels. After 9y, a more pronounced reduction in normalized CSA was observed in GMFCS-II&amp;III. Different trajectories in ML growth were shown between the GMFCS-level subgroups. These longitudinal trajectories could be used to monitor the SCP muscle pathology during childhood and to optimize treatment planning and goals aiming to stimulate muscle growth

The neurovascular niche is crucial for constant blood supply and blood-brain barrier (BBB) function and is altered in a number of different neurological conditions, making this an intensely active field of research. Brain vasculature is unique for its tight association of endothelial cells with astrocytic endfeet processes. Separation of the vascular compartment by centrifugation-based methods confirmed enrichment of astrocytic endfeet processes, making it possible to study the entire vascular niche with such methods. Several centrifugation-based separation protocols are found in the literature; however, with some constraints which limit their applicability and the scope of the studies. Here, we describe and validate a protocol for physically separating the neurovascular niche from the parenchyma, which is optimized for smaller tissue quantities. Using endothelial, neuronal and astrocyte markers, we show that quantitative Western blot-based target detection can be performed of both the vascular and parenchymal fractions using as little as a single mouse brain hemisphere. Validation of our protocol in rodent stroke models by detecting changes in serum albumin signals and astrocyte activation, i.e. increased glial fibrillary acidic protein expression, between the ipsilateral and the lesion-free contralateral hemisphere demonstrates this protocol as a new way of detecting BBB breakdown and astrogliosis, respectively.

Mammalian genomes encode tens of thousands of long-noncoding RNAs (lncRNAs), which are capable of interactions with DNA, RNA and protein molecules, thereby enabling a variety of transcriptional and post-transcriptional regulatory activities. Strikingly, about 40% of lncRNAs are expressed specifically in the brain in precisely regulated temporal and spatial expression patterns. In stark contrast to the highly conserved repertoire of protein-coding genes, thousands of new lncRNAs have appeared during primate nervous system evolution with hundreds of human-specific lncRNAs. Their evolvable nature and the myriad of potential functions make lncRNAs ideal candidates for drivers of human brain evolution. The human brain displays the largest relative volume of any animal species and the most remarkable cognitive abilities. In addition to brain size, structural reorganization and adaptive changes represent crucial hallmarks of human brain evolution. LncRNAs are increasingly reported to be involved in neurodevelopmental processes including proliferation, neurite outgrowth and synaptogenesis, as well as in neuroplasticity, suggested to underlie human brain evolution. Hence, evolutionary human brain adaptations are proposed to be essentially driven by lncRNAs, which will be discussed in this review.

Cerebral palsy is a group of nonprogressive conditions that affect movement and posture caused by damage to the central nervous system at an early stage of a child's development. Among this group of patients, there is a higher risk of the appearance and progression of neurogenic scoliosis, which unlike idiopathic scoliosis, progresses after skeletal maturity. The aim of the study was to analyze the association of comorbid factors with the risk of development and progression of neurogenic scoliosis. The study included 133 patients with cerebral palsy. The relationship between comorbidities in children with cerebral palsy and the risk of developing neurogenic scoliosis was demonstrated and proven.

Fisetin has been shown to be beneficial for brain injury and age-related brain disease via different mechanisms. The purpose of this study was to determine the presence of senescent cells and the effects of fisetin on cellular senescence in the brain and other organs in old sheep, a more translational model. Approximately 6-7 years old female sheep (N=6) were treated with 100mg/kg fisetin or vehicle two consecutive days a week for 8 weeks. All organs were harvested at the time of sacrifice. Histology, immunofluorescent staining, as well as Q-PCR was performed on different regions of brain tissues and organs. Our results indicated that Fisetin treatment at the current regimen did not affect general morphology of the brain. The presence of senescent cells in both cerebral brain cortex and cerebellum was detected by SA-β-Gal staining. More senescent cells were observed in the gray matter when compared to the white matter of the cerebral brain cortex. These senescent cells are mainly neurons in both gray and white matter of either cerebral brain cortex or cerebellum. Fisetin treatment showed a trend of decrease SA-β-Gal cells in gray matter of both cerebral brain cortex and cerebellum and significantly decreased in brain cortex white matter. Furthermore, fisetin treatment significantly decreased P16+ cells in brain cortex NEUN+ neurons, GFAP+ astrocytes, IBA+ microglia cells in both gray and white matter of cerebral brain cortex. Fisetin treatment also significantly decreased P16+ cells in microglia cells and a trend of decrease of P16+ cells in astrocytes in the non- (Cornu Ammonis) CA area of hippocampus. However, fisetin treatment did not change P16+ cells in the NEUN+ neurons in the CA1-4 area of the hippocampus. At the mRNA level, fisetin showed a decreased in GLB1 in heart ventricle muscle tissue and spleen tissues but not in other organs tested. Fisetin treatment also showed a decreased antioxidant gene SOD1 and increased CAT in spleen and bone marrow. Fisetin treatment showed variable effects in SASP and inflammasome genes in different organs. In conclusion, we found senescent cells are widely present in the cerebral brain cortex and cerebellum of old sheep. In addition, fisetin treatment decreased senescent cells as well as P16+ cells in the neurons in both gray and white matter of cerebral brain cortex and in astrocytes and microglia cells of cerebral brain cortex and non-CA area of hippocampus. Fisetin treatment represents a promising therapeutic strategy for age-related brain disease.

Cerebellar mutism syndrome (CMS), also known as posterior fossa syndrome, is encountered in a subset of children who have undergone an operative procedure of the posterior cranial fossa, mainly involving the vermis, and the most frequent underlying pathology is proved to be medulloblastoma. The most common characteristics of this syndrome include an often transient, although protracted, language impairment, emotional lability, along with cerebellar, and brainstem dysfunction. Nevertheless, a significant number of patients experience persistent neurological deficits and lasting neurocognitive impairment. A lot of research and clinical studies have been performed in order to better delineate this syndrome. The main obstacles in our way to highlight all aspects of this syndrome were related with an inconsistent nomenclature, poorly defined diagnostic criteria, and uncertainty surrounding risk factors and etiology. Currently, there is a combination of diagnostic criteria that are regarded as prerequisites in order to establish the diagnosis of CMS. These include language impairment and emotional lability, as proposed by the international Board of the Posterior Fossa Society in their consensus statement. Several risk factors are recognized as implicated in the pathogenesis of this syndrome, including midline tumor location, diagnosis of medulloblastoma, younger age at diagnosis, and preoperatively established language impairment. A proposed etiology of CMS includes disruption of the cerebellar outflow tracts, the cerebellar nuclei, and their efferent projections through the superior cerebellar peduncle. Specific treatment for CMS is lacking, and it continues to be directed at symptom management. Our aim is to present a comprehensive narrative review of CMS etiology, diagnosis, risk factors, clinical presentation, and clinical management. Moreover, we attempt to recognize the most widely recognized priorities of the research community in order to expand our knowledge in the era of diagnostics, prevention, and therapeutic options for patients suffering from CM, or who are at risk for development of this syndrome.

Malignant gliomas are the most common primary brain tumors in adults up to an extent of 78% of all primary malignant brain tumors. However, total surgical resection is almost unachievable due to considerable infiltrative ability of glial cells. The efficacy of current multimodal therapeutic strategies is, furthermore, limited by the lack of specific therapies against malignant cells, and, therefore, the prognosis these in patients is still very unfavorable. The limitation of conventional therapies, which may result from inefficient delivery of the therapeutic or contrast agent to brain tumors are major reasons for this unsolved clinical problem. The major problem in brain drug delivery is the presence of the blood brain barrier which limits the delivery of many chemotherapeutic agents. Nanoparticles, thanks to their chemical configuration, are able to go through the blood-brain barrier carrying drugs or genes targeted against gliomas. Carbon nanomaterials show distinct properties including electronic properties, penetrating capability on the cell membrane, high drug-loading and pH-dependent therapeutic unloading capacities, thermal properties, large surface area and easy modification with molecules, which render them as a suitable candidate to deliver drugs. In this review we will focus on the potential effectiveness of the use of carbon nanomaterials in the treatment of malignant gliomas discussing the current progress of in vitro and in vivo researches of carbon nanomaterials-based drug delivery to brain.

Thoracic aortic and arterial aneurysms are cardiovascular conditions associated with life-threatening endpoints including dissection and rupture. The genetic basis underlying the development these disease states is an evolving field, and the reporting of variants associated with aneurysms in patients are essential for advancing screening and diagnostic tools. Among all patients in our program who underwent clinical genetic screening (N=145) for arterial aneurysm and dissection disorders, we identified three patients with single nucleotide variants in the TNXB gene. This gene has known roles in collagen fibrillogenesis and classic Ehlers Danlos Syndrome. This is one of the first reports to associate this gene with aortopathy/arteriopathy and advances the literature relating extracellular matrix genes to arterial aneurysm development.

Synaptic transmission is essential for nervous system function and the loss of synapses is a known major contributor to dementia. Alzheimer’s disease dementia (ADD) is characterized by synaptic loss in the mesial temporal lobe and cerebral neocortex, brain areas associated with memory and cognition. The association of synaptic loss and ADD was established in the late 1980s and it has been estimated that 30-50% of neocortical synaptic protein is lost in ADD, but there has not yet been a quantitative profiling of different synaptic proteins in different brain regions in ADD from the same individuals. Very recently, PET imaging of synapses is being developed, accelerating the focus on the role of synaptic loss in ADD and other conditions. In this study, we quantified densities of two synaptic proteins, the presynaptic protein SNAP25 and the postsynaptic protein PSD95 in human brain using enzyme-linked immunosorbent assays (ELISA). Protein was extracted from the cingulate, hippocampus, frontal, visual, and entorhinal cortex from cognitively unimpaired controls, subjects with mild cognitive impairment (MCI) and demented subjects with different levels of Alzheimer’s pathology. SNAP25 is significantly reduced in ADD when compared to controls in frontal cortex, visual cortex and cingulate; while hippocampus showed a smaller, non-significant reduction and entorhinal cortex concentrations were not different. In contrast, all brain areas showed lower PSD95 concentrations in ADD when compared to non-demented controls, although in hippocampus this failed to reach significance. Interestingly, cognitively unimpaired cases with high levels of AD pathology had higher levels of both synaptic proteins in all brain regions. SNAP25 and PSD95 concentrations significantly correlated with densities of neurofibrillary tangles, amyloid plaques and Mini Mental State Examination scores. Our results suggest that synaptic transmission is affected by ADD in multiple brain regions. Differences were less marked in entorhinal cortex and hippocampus, most likely due to a ceiling effect imposed by the very early development of neurofibrillary tangles in older people in these brain regions.

The intracranial pressure (ICP) signal, as monitored on patients in intensive care units, contains pulses of cardiac origin where P1 and P2 subpeaks can often be observed. When calculable, the ratio of their relative amplitudes is an indicator of the patient’s cerebral compliance. This characterization is particularly informative on the overall state of the cerebrospinal system. We developed a recurrent neural network-based framework for P2/P1 ratio computation that only takes a raw ICP signal as an input. Two tasks are performed, namely pulse classification and subpeak designation. Pulse classification was achieved with an area under the curve of 0.90 on a 4,344-pulse testing dataset, while the peak designation algorithm identified pulses with a P2/P1 ratio > 1 with a 97.3% accuracy. Although it still needs to be evaluated on a larger number of labeled recordings, our automated P2/P1 ratio calculation framework appears to be a promising tool for improving bedside monitoring devices.

Focal cerebral ischemia can lead to blood-brain barrier (BBB) breakdown, which is implicated in neuroinflammation and elevation of matrix metalloproteinases (MMPs). The role of the anti-inflammatory protein, monocyte chemotactic protein–induced protein 1 (MCPIP1) plays in the injury of BBB in stroke has not yet been reported. This study was conducted to identify and characterize the role MCPIP1 plays in BBB breakdown. Transient middle cerebral artery occlusion (MCAO) is induced in both wild-type and Mcpip1^-/- mice for 2 hours of occlusion periods followed by reperfusion for 24 or 48 hours. BBB permeability was measured by FITC-dextran extravasation, MMP-9/3 expression was analyzed by western blot, and claudin-5 and zonula occludens-1 (ZO-1) were analyzed by immunohistochemistry and western blot. After MCAO in wild type mouse is induced, there is significantly increase in MCPIP1 mRNA and protein levels. Absence of MCPIP1 leaded to significant increase in FITC-dextran leakage in peri-infarct brain, significant upregulation of MMP-9, MMP-3 and reduced levels of tight junction components, claudin-5 and ZO-1 in the brain after MCAO. Our data demonstrate that absence of MCPIP1 exacerbates ischemia-induced blood-brain barrier disruption by enhancing the expression of matrix metalloproteinases and degradation of tight junction proteins. Overall data indicate that MCPIP1 is important protective role against BBB disruption in cerebral ischemia.

Dextro-transposition of the great arteries (D-TGA) is a critical congenital heart defect that can impact neurodevelopment due to cerebral perfusion and oxygenation disorders. Materials and Methods: In a retrospective study conducted at a tertiary center between 2016 and 2023, we investigated the early effects of Prostaglandin E1 (PGE1) administration and balloon atrial septostomy (BAS) on cerebral blood flow and oxygenation in inborn neonates with D-TGA. Cerebral Doppler Ultrasound in the anterior cerebral artery (ACA) was performed to assess resistive index (RI), Peak Systolic Velocity (PSV), and End-Diastolic Velocity (EVD) before PGE1, before the BAS procedure and 24 hours after birth. Cerebral regional saturations of oxygen (crSO2) and cerebral fractional tissue oxygen extraction (cFTOE) were evaluated. D-TGA patients were divided into the PGE1 group and the PGE1+BAS group. Age-matched healthy controls were used for comparison. Results: All 83 D-TGA newborns received PGE1 within two hours after delivery, of whom 46 (55.42%) underwent BAS. 77 newborns composed the control group. PGE1 administration increased crSO2 from 47% to 50% in the PGE1 group but lower than in controls at 24 hours of life, while cFTOE remained elevated. The RI increased 24 hours after delivery (0.718 vs. 0.769; p=0.000002) due to decreased EDV (10.71 vs. 8.74; p&lt;0.0001) following PGE1 treatment. The BAS procedure resulted in a significant increase in crSO2 from 42% to 51% at 24 hours of life in the PGE1+BAS group. Doppler parameters exhibited a similar trend as observed in the PGE1 group. Conclusion: PGE1 treatment and BAS are lifesaving interventions that may improve cerebral perfusion and oxygenation in newborns with D-TGA during the transition period.

Diffuse optical tomography (DOT) technology enables a differentiation between oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) in the sensory and motor cerebral gyri, resulting in greater sensitivity for cerebral activation compared to functional magnetic resonance imaging (fMRI). Here, we introduce a novel approach where functional regions of interest (ROIs) are created based on the specific signal behavior observed in DOT measurements, in contrast to the conventional use of structural-ROIs obtained from anatomical information. The generation of cerebral activation maps involves using the general linear model (GLM) to compare the outcomes obtained from both the functional and structural ROI approaches. DOT-derived maps are then compared with maps derived from fMRI datasets considered the gold standard for assessing functional brain activity. The results obtained demonstrate the effectiveness of employing functional ROIs to improve the spatial location of functional activations in the sensory and motor cerebral gyri by leveraging the neural synchronization data provided by DOT. Furthermore, this methodology simplifies data processing in animal models, where anatomical differences compared to the human head can pose challenges. By incorporating functional ROIs prior to GLM application, this study offers enhancements to DOT analysis techniques and broadens its applicability in both human and animal models.

Objective: This study aimed to examine the relationship between health structure disparities and hospitalizations and deaths among the pediatric population in different regions. Method: The study employed an ecological time series design, utilizing population-based secondary data ob-tained from DATASUS, from the Brazilian Ministry of Health. The data included in this study encompassed the population aged zero to 19 years, health establishments, physicians working in health establishments, hospitalizations, and deaths related to Morbidities listed in the Interna-tional Classification of Diseases. The focus was explicitly on individuals diagnosed with Cere-bral Palsy and other paralytic syndromes. The data for this study were gathered from January 2018 to December 2021. TABNET was used for data collection, and Excel for tabulation and anal-ysis. Results: Analysis of health structure data across regions revealed notable disparities, par-ticularly in the North and Northeast regions, compared to other regions. These discrepancies prompted a decision to conduct a comparative assessment between these regions and the rest of the country. Conclusion: In the North region, a significant 50% difference in hospitalizations based on residence versus a place of care was observed for individuals with Cerebral Palsy and other paralytic syndromes, indicating the necessity for relocation to access appropriate medical treatment.

The affected upper limb in children with Unilateral Spastic Cerebral Palsy (US CP) has motor and somatosensory impairments, that contribute negatively to children’s bimanual performance and quality of life. Mirror Therapy (MT) is being studied to become an approachable intensive and home-based therapy, suitable for children with US CP. The aim of this study is to examine the feasibility of a 5-week home-based program of MT for children with US CP. Six children aged 8-12 years old performed the therapy, five days per week, 30 minutes per day. A minimum of an 80% of compliance was required. The evaluations included the feasibility of the therapy (compliance, total dosage, perceived difficulty of the exercises, and losses of follow-ups and evaluations), the bimanual performance, the somatosensory function and the quality of life at baseline, at the end of the intervention, and at 1-month follow-up. All children completed the therapy and were included in the analysis. The total accomplishment was 86.47 ± 7.67. The perceived difficulty of the exercises ranged from 2,37 to 4,51. As a conclusion, a home-based program of Mirror Therapy is suitable and feasible for children with US CP.

The contribution of genetic and environmental factors to the pathophysiology of cerebral aneurysms in monozygotic twins is under-reported and presents ambiguous arguments. The morphology and hemodynamics of neurovascular arteries in a pair of monozygotic twins (MTs) were investigated to reveal the underlying mechanisms. Four arterial models were reconstructed for the twin A-right brain and left brain, twin B-left brain, and B-left brain without anterior cerebral arteries based on preclinical scanned information. Subsequently, the dimensions, configurations and outlined curves of the three-perspective geometries were compared between the MTs. Adopting an in-vitro validated numerical cerebral aneurysm model, hemodynamic patterns were investigated and compared in the MT models, respectively. Morphological comparisons of the MTs show the size and shape of cerebral arteries exist significant differences, despite of the expected genetic similarities. These differences can be attributed to variations during embryological development and external environmental influences. Qualitatively and generally, numerical results indicate the MTs have some hemodynamic similarities (e.g., time-averaged pressure (TAP) distributions (~13400 Pa), and oscillatory shear index (0~0.49), but present significant differences in specific local arteries due to morphological variances. Specifically, the difference in the volumetric blood flow rate in corresponding arteries between the MTs is from 16% (smallest) in anterior choroidal artery (AChA) to 221% (largest) in the ophthalmic artery (OphA), varying with specific compared arteries. Also, the registered hemodynamic indicators, such as the maximum time-averaged wall shear stress (TWSS) (53.6 Pa vs. 37.8 Pa), and different local OSI distributions were observed between the MTs. The findings revealed that morphological variations in MTs could be generated by embryological and environmental factors, thus assuming they share the identical morphology in cardiovascular and neurovascular systems may lead to significant misevaluations in hemodynamics quantifications and further lesions.

Development of the central nervous system (CNS) depends on accurate spatiotemporal control of signalling pathways and transcription programs. Forkhead Box G1 (FOXG1) is one of the master regulators that plays fundamental roles in forebrain development, from the timing of neurogenesis to the patterning of the cerebral cortex. Mutations in the FOXG1 gene cause a rare neurodevelopmental disorder called FOXG1 syndrome, also known as congenital form of Rett syndrome. Patients presenting with FOXG1 syndrome manifest a spectrum of phenotypes ranging from severe cognitive dysfunction and microcephaly to social withdrawal and communication deficits with varying severities. To develop and improve therapeutic interventions, there has been considerable progress towards unravelling the multi-faceted functions of FOXG1 in neurodevelopment and pathogenesis of FOXG1 syndrome. Moreover, recent advances in genome editing and stem cell technologies, as well as increased yield of information from high throughput omics opened promising and important new avenues in FOXG1 research. In this review, we provide a summary of clinical features and emerging molecular mechanisms underlying FOXG1 syndrome, and explore disease-modelling approaches in animals and human-based systems to highlight prospects of research and possible clinical interventions.

A hemispheric asymmetry is known for the processing of global vs. local visual information. In this study, we investigated the existence of a hemispheric asymmetry for visual processing of low vs. high spatial frequency gratings. Event-related potentials were recorded in a group of healthy right-handed volunteers from 30 scalp sites. Six types of stimuli (1.5, 3 and 6 c/deg gratings) were randomly flashed 180 times in the left and right upper hemi-fields. Stimulus duration was 80 ms and ISI ranged between 850-1000 ms. Participants had to pay attention and respond to targets based on their spatial frequency and location, or to passively look at the stimuli. C1 and P1 visual responses, as well as a later Selection negativity and a P300 components of ERPs were quantified and subjected to repeated-measure ANOVAs. Overall, performance was faster for the RVF, thus suggesting a left hemispheric advantage for attentional selection of local elements. Similarly, the analysis of mean area amplitude of C1 (60-110 ms) sensory response showed a stronger attentional effect (F+L+ vs. F-L+) at left occipital areas, thus suggesting the sensory nature of this hemispheric asymmetry.

This study aimed to evaluate the early-childhood comorbidities of cerebral palsy (CP) in children with low birth weight (LBW) and assess the impact of maternal bio-psychosocial factors on the risk of CP in preterm infants across varying birth weights. Data for 15,181 prematurely born infants from 2009 to 2013 and 151,810 matched controls from Taiwan's National Health Insurance Research Database were analyzed. Period prevalence of CP, and comorbidities of LBW were verified, and odds ratios (ORs) were calculated. Results confirmed that increasing prematurity and low birth weight (LBW) rates in Taiwan. LBW was associated with higher CP prevalence. Maternal age extremes (&lt;20 and &gt;40 years) were significant risk factors of CP in LBW infants. LBW infants showed higher risks of respiratory, circulatory, and nervous system and psycho-developmental comorbidities compared to controls. Infants with the lowest birth weights had even higher ORs for these comorbidities. However, gastrointestinal and nutritional comorbidities were less prevalent in premature infants. Maternal factors such as family income, number of hospital admissions, and length of hospital stay were significantly correlated with birth weight and subsequent complications. Each additional gestational week significantly reduced the risk of complications in premature infants. Additionally, maternal bio-psychosocial factors were associated with birth weight and related outcomes in premature infants, emphasizing the importance of addressing these factors in prenatal care and interventions.

Ischemia stroke is one of a clinically common cerebrovascular disease. And Inhibition of brain tissue ischemia and reperfusion-induced damage, especially apoptosis, has an irreplaceable protective effect on ischemic nerves, and has special significance for the treatment of patients after treatment. However, the development of neuroprotective drugs still has certain challenges. Radix scrophulariae as a valuable medicine, has been discovered to has neuroprotective effects. Our researches initially proved that Radix scrophulariae aqueous extract (RSAE) exerting a neuroprotective effects on cerebral ischemia and reperfusion (I/R) injury in oxygen glucose deprivation and reperfusion (OGD/R)-induced PC12 cells and middle cerebral artery occlusion/reperfusion (MCAO/R) model mice, were associated with attenuation of infarct volume, brain water content, nitric oxide (NO) and malondialdehyde (MDA), inhibiting I/R-induced damage by reducing the levels of LDH release, improving anti-oxidant capacity by upregulating the SOD, GSH-Px and CAT activity, stabilizing mitochondrial membrane potential, reducing neuronal apoptosis, necrosis and neuronal loss by regulating the expression of anti-apoptotic BCL-2and pro-apoptotic protein Bax, and elucidating downregulate the phosphorylation levels of MAPK pathways. Our findings may elaborate the neuroprotective effects and potential mechanisms of RSAE on focal cerebral I/R injury in mice. Since, Radix scrophulariae, as a potential neuroprotective natural plant, has originally been identified to, our results may offer directions and clues for discovering new active compounds or drugs for treatment of ischemic stroke, which allows us to discover many new natural active chemicals by chemical separation and identification, and provide new insights into therapeutic targets in stroke patients.

Intraprocedural rupture (IPR) is a severe complication of coil embolization (CE) for intracranial aneurysms, yet the clinical and hemodynamic features of rupture risk areas remain unclear. From January 2013 to December 2023, 435 saccular cerebral aneurysms (316 unruptured, 119 ruptured) underwent CE at our institution. Included were cases where extravasation or coil protrusion occurred during CE. The rupture point was determined from postoperative data, and computational fluid dynamics (CFD) analysis was conducted to assess hemodynamic features. IPR occurred in six aneurysms (1.3%; three ruptured, three unruptured; dome size: 4.7±1.8 mm, D/N: 1.5±0.5, locations: four internal carotid artery [ICA], one anterior cerebral artery, one middle cerebral artery). ICA aneurysms were treated using adjunctive techniques (three balloon-assisted, one stent-assisted). Two aneurysms (M1M2 and A1) were treated simply, yet had relatively small and misaligned domes. CFD analysis identified the rupture point as a flow impingement zone with maximum pressure (Pmax) in five aneurysms (83.3%). Time-averaged wall shear stress (WSS) was locally reduced around this area (1.3±0.7 [Pa]). Hemodynamically unstable areas indicated fragile, thin walls with rupture risk. Microcatheter insertion along the inflow zone, directed towards the caution area, was practiced. The presence of a flow impingement zone with Pmax and low WSS suggests potential aneurysm rupture in CE, particularly with adjunctive techniques. Small aneurysms, especially those with axial misalignment, warrant careful consideration due to the risk of excessive flow impact stress on the aneurysm wall.

Not in the history of transmissible illnesses has there been an infection as strongly associated with acute cerebrovascular disease as the novel human coronavirus, SARS-CoV-2. While the risk of stroke has known associations with other viral infections, such as influenza and human immunodeficiency virus, the risk of ischemic and hemorrhagic stroke related to SARS-CoV-2 is unprecedented. Furthermore, the coronavirus disease 2019 (COVID-19) pandemic has so profoundly impacted psychosocial behaviors and modern medical care that we have witnessed shifts in epidemiology and have adapted our treatment practices to reduce transmission, address delayed diagnoses, and mitigate gaps in health care. In this narrative review, we summarize the history and impact of the COVID-19 pandemic on cerebrovascular disease, and lessons learned regarding the management of patients as we endure this period of human history.

Background: Anemia is one of the most frequent diseases worldwide, affecting a third of the general population. Anemia in general and in particular, iron-deficient anemia (IDA), has been associated to a higher risk of thrombotic manifestations, including ischemic stroke and cerebral venous thrombosis (CVT), as well as systemic extra cerebral arterial and venous thrombosis. Despite these data, anemia is seldom considered as an etiological factor of stroke. Methods: An individual case encompassing all known neurovascular and systemic arterial and venous thrombotic manifestations related to IDA is presented with the focus on clinical reasoning issues in the diagnostic pathways, starting from the neuroradiological signs. The main questions have been identified and addressed in a narrative review of the most relevant data in the literature from a pragmatic and clinical viewpoint. Results and Discussion: The presented case concerns a 46 years old man admitted to the Stroke Unit because of acute is-chemic stroke with multiple thrombi in large intracranial and extracranial vessels, multifocal ischemic lesions in several arterial territories and the concurrent finding of asymptomatic CVT, pulmonary embolism with lung infarction and aortic thrombosis. An extended diagnostic work-up excluded the main etiologies (arterial dissection, cardiac embolism, genetic and acquired prothrombotic disorders, as cancer and antiphospholipid syndrome), except for a severe IDA, such as to require blood transfusions followed by anticoagulant therapy for the several thrombotic manifestations. Neuroimaging and systemic vascular findings have been analyzed and the main issues proposed by the case in the diagnostic pathway have been identified and discussed in a pragmatic clinical road map reviewing the data provided by the literature. Conclusions: IDA is a common but treatable condition that, independently or synergically, may increase the risk of thrombotic events. The diagnostic and therapeutic approach has not yet defined and each case should be individually addressed in a pragmatic clinical road map.

Growing interest surrounds the assessment of perivascular spaces (PVS) on magnetic resonance imaging (MRI) and their validation as a clinical biomarker of adverse brain health. Nonetheless, the limits of validity of current state-of-the-art segmentation methods are still unclear. Here, we propose an open-source three-dimensional computational framework comprising 3D digital reference objects and evaluate the performance of three PVS filtering methods under various spatiotemporal imaging considerations (including sampling, motion artefacts, and Rician noise). Specifically, we study the performance of the Frangi, Jerman and RORPO filters in enhancing PVS-like structures to facilitate segmentation. Our findings were three-fold. First, as long as voxels are isotropic, RORPO outperforms the other two filters, regardless of imaging quality. Unlike the Frangi and Jerman filters, RORPO’s performance does not deteriorate as PVS volume increases. Second, the performance of all “vesselness” filters is heavily influenced by imaging quality, with sampling and motion artefacts being the most damaging for these types of analyses. Third, none of the filters can distinguish PVS from other hyperintense structures (e.g. white matter hyperintensities, stroke lesions, or lacunes) effectively, the area under precision-recall curve dropped substantially (Frangi: from 94.21 [IQR 91.60, 96.16] to 43.76 [IQR 25.19, 63.38]; Jerman: from 94.51 [IQR 91.90, 95.37] to 58.00 [IQR 35.68, 64.87]; RORPO: from 98.72 [IQR 95.37, 98.96] to 71.87 [IQR 57.21, 76.63] without and with other hyperintense structures, respectively). The use of our computational model enables comparing segmentation methods and identifying their advantages and disadvantages, thereby providing means for testing and optimising pipelines for ongoing and future studies.

The New Zealand brushtail possum (Trichosurus vulpecula), introduced from Australia in the 1850s, is an invasive species that is widespread throughout New Zealand and forms the largest self-sustained reservoir of bovine tuberculosis (Mycobacterium bovis) in the wild. Conservation and agricultural authorities regularly apply a series of population control measures to suppress brushtail possum populations. The evolutionary consequence of more than half a century of intensive population control operations on the species genomic diversity and population structure is hindered by a paucity of available genomic resources for the species. This study is the first to characterise the functional content and diversity of brushtail possum liver and brain cerebral cortex transcriptomes. Raw sequences from hepatic cells and cerebral cortex were assembled into 58,001 and 64,735 transcripts in hepatic cells and cerebral cortex, respectively. Functional annotation and polymorphism assignment of the assembled transcripts demonstrated a considerable level of variation in the core metabolic pathways that represent potential targets for selection pressure exerted by chemical toxicants. This study suggests that the brushtail possum population in New Zealand harbours considerable levels of variation in metabolic pathways that could potentially promote the development of tolerance against chemical toxicants.

Survivors of severe brain injury may require care in a neurointensive care unit (neuro-ICU), where the brain is vulnerable to secondary brain injury. Thus, there is a need for noninvasive, bedside, continuous cerebral blood flow monitoring approaches in the neuro-ICU. Our goal is to address this need through combined measurements of EEG and functional optical spectroscopy (EEG-Optical) instrumentation and analysis to provide a complementary fusion of data about brain activity and function. The present case demonstrates in a patient with traumatic brain injury, noninvasive cerebral blood flow transients can be recorded that correlate with gold-standard invasive measurements and with the frequency content changes in the EEG data during clinical care.

Brain death (BD) concept has been increasingly widely accepted beginning since the late 1950s, but several controversies have appeared when intracranial pathology is localized to the posterior fossa. In the presence of a primary supratentorial brain lesion, a severe forebrain lesion is combined with either the subsequent gradual loss of brainstem function, due to rostrocaudal transtentorial brain herniation. In secondary brain lesions (i.e., cerebral hypoxia), the brainstem is also affected like the forebrain. However, a minority of patients with a primary infratentorial brain lesion (i.e., basilar artery thrombosis or brainstem or cerebellar bleeds) may retain cerebral blood flow and EEG activity. In this article I discuss that if a brainstem lesion does not provoke a massive increase of intracranial pressure there may be no complete cerebral circulatory arrest, explaining the preservation of EEG activity, evoked potentials, and autonomic function. I also discuss the case of Jahi McMath who was declared brain-dead, but ancillary tests, performed 9 months after initial brain insult, showed conservation of intracranial structures, EEG activity, and autonomic reactivity to “Mother Talks” stimulus, rejecting the diagnosis of BD. Jahi McMath’s MRI study demonstrated a huge lesion in the pons. Some authors have argued that in patients with primary brainstem lesions it might be possible to find a in some cases partial recover of consciousness, even fulfilling clinical BD criteria. This was the case in Jahi McMath. Further research and discussion are necessary about the use of ancillary tests in BD diagnosis in primary posterior fossa lesions.

Alzheimer’s disease (AD), the most common cause of dementia, is characterized by disruptions in memory, cognition, and personality, significantly impacting morbidity and mortality rates among older adults. However, the exact pathophysiological mechanism of AD remains unknown, and effective treatment options for AD are still lacking. Human induced pluripotent stem cells (iPSC) are emerging as promising platforms for disease research, offering the ability to model genetic mutations associated with various conditions. Patient-derived iPSCs are useful for modeling neurodegenerative and neurodevelopmental disorders. In this study, we generated AD iPSCs from peripheral blood mononuclear cells obtained from a 65-year-old patient with AD carrying the E682K mutation in the amyloid precursor protein (APP) gene. Cerebral organoids derived from AD iPSCs recapitulated the AD phenotype, exhibiting significantly increased levels of tau protein. Our analysis revealed that an iPSC disease model of AD is a valuable assessment tool for pathophysiological research and drug screening.

Cerebral cavernous malformations (CCM) or familial cavernomatosis is a rare, autosomal dominant, inherited disease characterized by the presence of vascular malformations consisting of blood vessels with an abnormal structure in the form of clusters. Based on the altered gene (CCM1/Krit1, CCM2, CCM3) and its origin (spontaneous or familial), different types of this dis-ease can be found. In this work we have isolated and cultivated primary endothelial cells (ECs) from peripheral blood of a type 1 CCM patient. Differential functional and gene expression pro-file of these cells were analyzed and compared to primary ECs from a healthy donor. The muta-tion of the familial index case consisted of a heterozygous point mutation in the position +1 splicing consensus between exons 15 and 16, causing failure in RNA processing and in the final protein. Furthermore, gene expression analysis by quantitative PCR revealed a decreased ex-pression of genes involved in intercellular junction formation, angiogenesis, and vascular ho-meostasis. Cell biology analysis showed that CCM1 ECs were impaired in angiogenesis and cell migration. Taken together, the results obtained suggest that the alterations found in CCM1 ECs are already present in the heterozygous condition, suffering from vascular impairment and someway predisposed to vascular damage.

In recent years, there has been a growing interest in the preoperative modeling of fluid-structure interaction in the treatment of cerebral aneurysms. In this study, we investigate two cases involving laminar incompressible fluid flow interacting with hyperelastic materials (a vertical flap and aneurysm walls) under the effect of fluid flow. We present a finite element method (FEM) for these prototypical two-dimensional ($2D$) configurations, taking into account the complex flows and deformation of the variant's structure models. We use an Arbitrary Lagrangian-Eulerian (ALE) formulation in a continuum, fully monolithic coupled way, and discretize the fluid and solid domains using the quadratic LBB stable $P_2P_1$ finite element pair to approximate the displacement, velocity, and pressure spaces independently. The resulting discretized form of the nonlinear algebraic system is linearized using a variant of Newton's procedure, and the Jacobian matrices are approximated via the divided difference method. The resulting linear systems are solved using a direct solver MUMPS. We evaluate hydrodynamic forces such as drag and lift coefficients for nonlinear elastic material models, including Saint-Venant Kirchoff, Neo-Hookean, and Mooney-Rivlin (2 parameters) separately. To gain more physical insight into the problem, we verify the computed results by comparing the velocity, viscosity, and pressure fields. Our aim is to qualitatively analyze the changes in the mechanics of the wall behavior of the elasticity of the flap vs. the complexity of deformation, interface, details for prototypical flow situations, corresponding displacement, and deformation. We also provide a physical interpretation of blood flow magnitude and basic hemodynamic phenomena of wall shear stresses (WSS) in aneurysma and the range of deformation. Overall, this study presents a comprehensive approach to modeling fluid-structure interaction in cerebral aneurysms, which could help in the development of more effective treatment strategies.

As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”

Dynamic contrast-enhanced MRI (DCE-MRI) is increasingly used to quantify and map the spatial distribution of blood-brain barrier (BBB) leakage in neurodegenerative disease, including cerebral small vessel disease and dementia. However, the subtle nature of leakage and resulting small signal changes make quantification challenging. While simplified one-dimensional simulations have probed the impact of noise, scanner drift, and model assumptions, the impact of spatio-temporal effects such as gross motion, k-space sampling and motion artefacts on parametric leakage maps has been overlooked. Moreover, evidence on which to base the design of imaging protocols is lacking due to practical difficulties and the lack of a reference method. To address these problems, we present an open-source computational model of the DCE-MRI acquisition process for generating four-dimensional Digital Reference Objects (DROs), using a high-resolution brain atlas and incorporating realistic patient motion, extra-cerebral signals, noise and k-space sampling. Simulations using the DROs demonstrated a dominant influence of spatio-temporal effects on both the visual appearance of parameter maps and on measured tissue leakage rates. The computational model permits a greater understanding of the sensitivity and limitations of subtle BBB leakage measurement and provides a non-invasive means of testing and optimising imaging protocols for future studies.

Ménière's disease (MD) has an unclear cause. The microvascular dysregulation of the inner ear has been increasingly pointed as a potential contributor. This study investigates the prevalence of cardiovascular risk factors (CVRFs) in MD patients compared to those with posterior circulation cerebral infarction (POCI). CVRFs like hypertension, diabetes, dyslipidemia, obesity, coronary heart disease, and smoking were assessed in both MD and POCI patients. Brain MRI identified POCI etiology as "small vessel occlusion" (SVO) or "other etiology" (OE). The study included 64 MD and 84 POCI patients. Compared to MD, POCI OE showed a higher prevalence of CVRFs across various age groups, including hypertension, diabetes, dyslipidemia, and smoking. Notably, the odds of having POCI OE were significantly higher for individuals with hypertension and smoking. On the other hand, POCI SVO showed similar prevalence of CVRFs compared to MD. This study reveals no significant difference in CVRF prevalence between MD and smaller vessel POCI. However, a clear distinction emerges when comparing MD to POCI with involvement of larger blood vessels. Further research is needed to confirm these findings and explore potential shared risk factors between POCI (SVO) and MD.

Magnetic resonance elastography (MRE) has revealed sexual dimorphism in brain stiffness in healthy individuals and multiple sclerosis (MS) patients. In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), we showed previously that inflammation-induced brain softening was associated with alterations of the extracellular matrix (ECM). However, it remained unclear whether the brain ECM presents sex-specific properties that can be visualized by MRE. Therefore, we aimed here at quantifying sexual dimorphism in brain viscoelasticity in association with ECM changes in healthy and inflamed brains. Multifrequency MRE was applied to the midbrain of healthy and EAE mice of both sexes to quantitatively map regional stiffness. To define differences in brain ECM composition, gene expression of the key basement membrane components laminin (Lama4, Lama5), collagen (Col4a1, Col1a1) and fibronectin (Fn1) was investigated by RT-qPCR. We showed that the healthy male cortex expressed less Lama4, Lama5, Col4a1 but more Fn1 (all p < 0.05) than the healthy female cortex, which was associated with 9% softer properties (p = 0.044) in that region. At peak EAE, cortical softening was similar in both sexes compared to healthy tissue, with an 8% difference remaining between males and females during EAE (p < 0.001). Cortical Lama4, Lama5 and Col4a1 expression increased 2 to 3-fold in EAE in both sexes while Fn1 decreased only in males (all p < 0.05). No significant sex differences in stiffness were detected in other brain regions. In conclusion, sexual dimorphism in the ECM composition of cortical tissue in the mouse brain is reflected by in vivo stiffness measured with MRE and should be considered in future studies by sex-specific reference values.

Stroke remains a major cause of death and disability in the United States and around the world. Solid safety and efficacy profiles of novel stroke therapeutics have been generated in the laboratory, but most failed in clinical trials. Investigations into the pathology and treatment of the disease remain a key research endeavor in advancing scientific understanding and clinical applications. In particular, cell-based regenerative medicine, specifically stem cells transplantation, may hold promise as stroke therapy because grafted cells and their components may recapitulate the growth and function of the neurovascular unit, which arguably represents the alpha and omega of stroke brain pathology and recovery. Recent evidence has implicated mitochondria, organelles with a central role in energy metabolism and stress response, in stroke progression. Recognizing that stem cells offer a source of healthy mitochondria, potentially transferrable into ischemic cells, may provide a new therapeutic tool. To this end, deciphering cellular and molecular processes underlying dysfunctional mitochondria may reveal innovative strategies for stroke therapy. Here, we review recent studies capturing the intimate participation of mitochondrial impairment in stroke pathology, and showcase promising methods of healthy mitochondria transfer into ischemic cells, to critically evaluate the potential of mitochondria-based stem cell therapy for stroke.

Fragile X Syndrome (FX) is the most common form of inherited cognitive impairment and falls under the broader category of Autism Spectrum Disorders (ASD). FX is caused by a CGG trinucleotide repeat expansion in the non-coding region of the X-linked Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene, leading to its hypermethylation and epigenetic silencing. Animal models of FX rely on the deletion of the Fmr1 gene which fail to replicate the epigenetic silencing mechanism of the FMR1 gene seen in human patients. Human stem cells carrying FX repeat expansions have provided a better understanding of the basis of the epigenetic silencing of FMR1. Previous studies have found that 5-Azacytidine (5Azac) can reverse this methylation; however, 5Azac can be toxic and may limit its therapeutic potential. Here, we show that the dietary factor Ascorbic Acid (AsA) can reduce DNA methylation in the FMR1 locus and lead to an increase in FMR1 gene expression in FX iPSCs and cerebral organoids. In addition, AsA treatment rescued neuronal gene expression and the morphological defects observed in FX iPSC-derived cerebral organoids. Hence, we demonstrate that the dietary co-factor AsA can partially revert molecular and morphological defects seen in human FX models in vitro. Our findings have implications for the development of novel therapies for FX in the future.

Viral infections leading to inflammation have been implicated in several common diseases such as Alzheimer’s disease (AD) and type 1 diabetes (T1D). Of note, herpes simplex virus 1 (HSV-1) has been reported to be associated with AD. We sought to identify the transcriptomic changes due to HSV-1 infection and anti-viral drug (acyclovir, ACV) treatment of HSV-1 infection in dissoci-ated cells from human cerebral organoids (dcOrgs) versus stem cell-derived pancreatic islets (sc-islets) to gain potential biological insights into the relevance of HSV-1-induced inflammation in AD and T1D. We observed that differentially expressed genes (DEGs) in HSV-1-infected sc-islets were enriched for genes associated with several autoimmune diseases, most significantly T1D but also rheumatoid arthritis, psoriasis, Crohn’s disease, and multiple sclerosis, whereas DEGs in HSV-1-infected dcOrgs were exclusively enriched for genes associated with AD. ACV treatment of sc-islets did not rescue transcript expression of autoimmune disease-associated genes. Finally, we identified gene ontology categories that were enriched for DEGs that were in common across, or unique to, viral treatment of dcOrgs and sc-islets, such as categories involved in the transferase complex, mitochondrial and autophagy function. Collectively, this studies pro-vide insight to the molecular effects of inflammation in AD and T1D.

Abstract: The recently described perivascular unit (PVU) resides immediately adjacent to the true capillary neurovascular unit (NVU) in the postcapillary venule and contains the normal-benign perivascular spaces (PVS) and pathological enlarged perivascular spaces (EPVS). The PVS are important, in that, they also have recently been identified to be the construct and the conduit responsible for the delivery of metabolic waste from the interstitial fluid to the ventricular cerebrospinal fluid for disposal into the systemic circulation and has been termed the glymphatic system. Importantly, the outermost boundary of the PVS is lined by protoplasmic perivascular astrocyte endfeet (pvACef) that communicate with regional neurons. As compared to the well-recognized and described neurovascular unit (NVU) and NVU coupling, the PVU is less well understood and remains an emerging concept. The primary focus of this narrative review is to compare the similarities and differences between these two units and discuss each of their structural and functional relationships and how they relate not only to brain homeostasis but also how they may relate to the development of multiple clinical neurological disease states and specifically how they may relate to obesity, metabolic syndrome, and type 2 diabetes mellitus. Additionally, the concept and importance of a perisynaptic astrocyte coupling to the neuronal synapses with pre- and postsynaptic neurons will also be considered as a perisynaptic unit to provide for the creation of the information transfer in the brain via synaptic transmission and brain homeostasis. Multiple electron microscopic images and illustrations will be utilized in order to help explain these complex units.

Technological advances in game-mediated robotics provide an opportunity to engage children with cerebral palsy (CP) and other neuromotor disabilities in more frequent and intensive therapy by making personalized, programmed interventions available 24/7 in children’s homes. Though shown to be clinically effective and feasible to produce, little is known of the subjective factors impacting acceptance of what we term assistive/rehabilitative (A/R) gamebots by their target populations. This research describes the conceptualization phase of an effort to develop a valid and reliable instrument to guide the design of A/R gamebots. We conducted in-depth interviews with 8 children with CP and their families who had trialed an exemplar A/R gamebot, PedBotHome, for 28 days in their homes. The goal was to understand how existing theories and instruments were either appropriate or inappropriate for measuring the subjective experience of A/R gamebots. Key findings were the importance of differentiating the use case of therapy from that of assistance in rehabilitative technology assessment, the need to incorporate the differing perspectives of children with CP and those of their parents into A/R gamebot evaluation, and the potential conflict between the goals of preserving the quality of the experience of game play for the child while also optimizing the intensity and duration of therapy provided during play.

In advanced world stroke is one of the disabling cause of death that can be managed with thrombolysis if presents early despite further risk of intracerebral haemorrhage. Secondary prevention is an important objective in ischaemic stroke where recurrence is very high with subsequent stroke. Carotid End Arterectomy impact a definitive and effective role for both symptomatic and asymptomatic carotid stenosis for secondary stroke prevention in selective cases. Thrombolysis is a potential primary management for certain group whereas carotid surgery employs secondary preventative measure in a specified ischaemic stroke group.