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Preprint REVIEW | doi:10.20944/preprints202306.0139.v1

Neurotrophic Viruses in the Pathogenesis of ALS

Jay Lombard, Andres D. Klein

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: ALS; TDP-43; misfolded proteins; enterovirus; polio; motor neurons; retrotransposons; prions; Alzheimer’s

Online: 2 June 2023 (05:43:02 CEST)

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Preprint REVIEW | doi:10.20944/preprints202306.0090.v1

Hybrid PET/MRI in Neuro-oncology: Current Status and Perspectives

Karl-Josef Langen, Norbert Galldiks, Jörg Mauler, Martin Kocher, Christian P. Filss, Gabriele Stoffels, Claudia Regio-Brambilla, Carina Stegmayr, Antje Willuweit, Wieland A. Worthoff, Jon Shah, Christoph Lerche, Felix Mottaghy, Philipp Lohmann

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: brain tumor diagnosis; PET; radiolabeled amino acids; O-(2-[18F]fluoroethyl)-L-tyrosine (FET); Hybrid PET/MRI; multimodal imaging

Online: 1 June 2023 (12:54:09 CEST)

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Advanced MRI methods and PET using radiolabeled amino acids provide valuable information in addition to conventional MR imaging for brain tumor diagnostics. These methods are particularly helpful in challenging situations such as the differentiation of malignant processes from benign lesions, the identification of non-enhancing glioma subregions, the differentiation of tumor progression from treatment-related changes, and the early assessment of response to anticancer therapy. The debate over which of the methods is preferable in which situation is ongoing and has been addressed in numerous studies. Currently, most radiology and nuclear medicine departments perform these examinations independently of each other leading to multiple examinations for the patient. The advent of hybrid PET/MRI allowed a convergence of the methods but to date simultaneous imaging has reached little relevance in clinical neuro-oncology. This is partly due to the limited availability of hybrid PET/MRI scanners, but is also due to the fact that PET is a second-line examination in brain tumors. PET is only required in equivocal situations, and spatial co-registration of PET examinations of the brain to previous MRI is possible without disadvantage. A key factor for the benefit of PET/MRI in neuro-oncology is a multimodal approach that provides decisive improvements in the diagnostics of brain tumors compared with a single modality. This systematic review focuses on studies that were able to demonstrate the additive value of amino acid PET and ‘advanced’ MRI in the diagnosis of brain tumors. Available studies suggest that the combination of amino acid PET and advanced MRI improves grading and the histomolecular characterization of newly diagnosed tumors. However, data concerning the delineation of tumor extent and biopsy guidance are of limited value. A clear additive diagnostic value of amino acid PET and advanced MRI can be achieved regarding the differentiation of tumor recurrence from treatment-related changes. Here, PET-guided evaluation of advanced MR methods seems to be helpful. In summary, there is growing evidence that a multimodal approach can achieve decisive improvements in the diagnostics of brain tumors, for which hybrid PET/MRI offers optimal conditions.

Preprint REVIEW | doi:10.20944/preprints202306.0076.v1

Treatable Myopathies

Genevieve Gucci Grace Capispisan Uy, Raymond Lotilla Rosales, Satish Khadilkar

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: myopathies; myositis; autoimmune; infectious

Online: 1 June 2023 (09:17:11 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202306.0050.v1

Neuron-Specific Enolase (NSE) as a Biomarker for Autistic Spectrum Disease (ASD)

Felician Stancioiu, Raluca Bogdan, Radu Dumitrescu

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: ASD; autism; autistic spectrum disease; NSE; Neuron-specific enolase; autism biomarker; neuroinflammation; neuronal apoptosis; mTOR

Online: 1 June 2023 (07:30:35 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202305.2264.v1

Chronic Fatigue Syndrome and Multiple Sclerosis have Reduced Craniospinal Compliance and Dilated Pressurized Bridging Cortical Veins: A Hypothesis Illustrated with Two Case Studies

Grant Bateman, Alexander Bateman

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Chronic fatigue syndrome; myalgic encephalomyelitis; multiple sclerosis; cortical vein; venous pressure

Online: 31 May 2023 (14:31:49 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.2199.v1

Exploring the Molecular Targets for the Antidepressant and Antisuicidal Effects of Ketamine Enantiomers by using Network Pharmacology and Molecular Docking

Glorister A. Altê, Ana Lúcia S. Rodrigues

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: esketamine; arketamine; bioinformatical analysis; depression; suicide

Online: 31 May 2023 (08:24:53 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.2172.v1

The Contribution of Sleep Texture in the Characterization of Sleep Apnea

Carlotta Mutti, Irene Pollara, Anna Abramo, Margherita Soglia, Clara Rapina, Carmela Mastrillo, Francesca Alessandrini, Ivana Rosenzweig, Francesco Rausa, Silvia Pizzarotti, Marcello luigi Salvatelli, Giulia Balella, Liborio Parrino

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: cyclic alternating pattern; sleep texture; sleep apnea; polysomnography

Online: 31 May 2023 (05:32:49 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1927.v1

Impacts of COVID-19 Pandemic on Seizure Control in Children with Epilepsy

Ja Un Moon, Da Hye Yoon, Min Ho Jung

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: COVID19; Children; Epilepsy; Adolescents; Pediatric; Pandemic

Online: 26 May 2023 (11:00:40 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1917.v1

Serum Biomarker Concentrations on Admission in Acute Traumatic Brain Injury: Associations with, TBI Severity, Toxoplasma gondii Infection and Outcome in a Referral Hospital Setting, Cameroon

Franklin Chu Buh, Germaine Sotoing Taiwe, Firas H. Kobeissy, Kevin W. Wang, Andrew I.R. Maas, Basil Kum Meh, Motah Mathieu, Eric Youm, Peter J.A. Hutchinson, Irene Ule Ngole Sumbele

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Serum biomarkers; Traumatic brain injury; CT-scan findings; outcome; Toxoplasma gondii

Online: 26 May 2023 (10:28:07 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1864.v1

Perspectives and Implications of Coanda Effect in Aneurysms

Vicentiu Mircea Saceleanu, Razvan-Adrian Covache-Busuioc, Luca Andrei Glavan, Antonio Daniel Corlatescu, Alexandru Vlad Ciurea

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Coanda Effect; aneurysm; hemodynamics; Willis Polygon; pathology

Online: 26 May 2023 (05:26:59 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1784.v1

CSF Soluble TREM2 Concentrations Correlate With the Severity of Neurofibrillary Degeneration, Cognitive Impairment, and Inflammasome Activation in Alzheimer’s Disease

Ena Španić Popovački, Mirjana Babić Leko, Lea Langer Horvat, Klara Brgić, Željka Vogrinc, Marina Boban, Nataša Klepac, Fran Borovečki, Šimić Goran

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Alzheimer’s disease; cerebrospinal fluid; inflammasome; microglia; mild cognitive impairment; plasma; tau protein; TREM2

Online: 25 May 2023 (09:40:33 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.1615.v1

Restoring Homeostasis as a Promising Therapeutic Strategy for Obesity and Sleep Disorders

Vijay Kumar, Shampa Ghosh, Pradeep Kumar Mishra, Areeba Aziz, Rachna Mehta, Jitendra Kumar Sinha

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Anti-obesity drugs; BMI; Glucose tolerance; Homeostasis; Obesity; Sleep disturbances; Molecular pathology

Online: 23 May 2023 (08:15:14 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.1549.v1

The Heterogeneous Progressive Multiple Sclerosis Lesion. How Can We Assess and Modify a Degenerating Lesion?

Olivia Ellen, Sining Ye, Danica Nheu, Mary Dass, Maurice Pagnin, Ezgi Ozturk, Paschalis Theotokis, Nikolaos Grigoriadis, Steven Petratos

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: multiple sclerosis; oligodendrocyte; myelination; inflammation; microglia; macrophage; bi-omarkers; imaging diagnostics

Online: 23 May 2023 (03:39:19 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.1444.v1

GABA Receptor Subtypes Involvement of Analgesia: Current Status

Xunjia Qian, Xinyi Zhao, Lulu Yu, Yujian Yin, Xiao-Dan Zhang, Liyun Wang, Jialie Luo, Jun-Xu Li, Qing Zhu

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Gamma-aminobutyric acid; subtype; analgesic effect; mechanism

Online: 19 May 2023 (15:03:06 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1315.v1

Peripheral Nerve Ultrasound for the Differentiation between ALS, Inflammatory and Hereditary Polyneuropathies

Annkatrin Hildebrand, Frank Schreiber, Luisa Weber, Philipp Arndt, Cornelia Garz, Susanne Petri, Johannes Prudlo, Sven G. Meuth, Yannic Waerzeggers, Solveig Henneicke, Stefan Vielhaber, Stefanie Schreiber

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: peripheral nerve ultrasound; tibial nerve; amyotrophic lateral sclerosis; inflammatory neuropathy; hereditary neuropathy; cross-sectional area; nerve microvascular blood flow

Online: 18 May 2023 (09:42:40 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.0098.v2

Therapeutic Potential of Heterocyclic Compounds Targeting Mitochondrial Calcium Homeostasis and Signaling in Alzheimer’s Disease and Parkinson’s Disease

Victor Tapias, Paula González-Andrés, Laura F. Peña, Asunción Barbero, Lucía Núñez, Carlos Villalobos

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Alzheimer’s disease; Parkinson’s disease; mitochondria; oxidative stress; calcium; heterocyclic compounds

Online: 17 May 2023 (14:13:20 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.1229.v1

Unraveling Molecular and Genetic Insights into Neurodegenerative Diseases: Advances in Understanding Alzheimer's, Parkinson's, ALS, and Huntington's Disease

Alexandru Vlad Ciurea, Aurel George Mohan, Razvan-Adrian Covache-Busuioc, Horia Petre Costin, Luca Andrei Glavan, Antonio Daniel Corlatescu, Vicentiu Mircea Saceleanu

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Molecular Genetics; Neurodegenerative Disease; Molecular pathology; Epigenetics; Gene expression; Therapeutic targets; Biomarkers; Alzheimer’s Disease; Parkinson’s Disease; Huntington Disease; Amyotrphic Lateral Sclerosis

Online: 17 May 2023 (10:28:26 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1182.v1

Low-Noise Amplifier and Neurostimulator in submicron CMOS for Closed-Loop Deep-Brain Stimulation (CLDBS)

Tiago Matheus Nordi, Rodrigo Henrique Gounella, Gabriel Augusto Ginja, Márcio Luis Amorim, Maximiliam Luppe, João Navarro Junior, Erich Talamoni Fonoff, Eduardo Colombari, Joao Paulo Carmo

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: CMOS; Closed Loop Deep-Brain Stimulation (CLDBS); Low Noise Amplifier (LNA); Neurostimulation; Implantable Devices

Online: 17 May 2023 (04:27:59 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.1105.v1

Evaluation of Consciousness Rehabilitation via Neuroimaging Methods

Jianyang Wang, Xinyu Gao, Zuchao Xiang, Fangfang Sun, Yong Yang

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: disorders of consciousness; EEG; fMRI; PET; fNIRS; multimodal

Online: 16 May 2023 (05:38:12 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.1068.v1

Potential Roles for the GluN2D NMDA Receptor Subunit in Schizophrenia

Chitra Vinnakota, Matthew Hudson, Nigel C Jones, Suresh Sundram, Rachel A Hill

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: GluN2D; Schizophrenia; NMDA receptor; NMDAR antagonists

Online: 16 May 2023 (03:06:00 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.0940.v1

Genetic Basis of Inflammatory Demyelinating Diseases of the Central Nervous System: Multiple Sclerosis and Neuromyelitis Optica Spectrum

Genaro Gabriel Ortiz, Blanca M.G. Torres-Mendoza, Javier Ramírez-Jirano, Jazmin Marquez-Pedroza, José J. Hernández-Cruz, Mario A. Mireles-Ramirez, Erandis D. Torres-Sánchez

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: multiple sclerosis; neuromyelitis optica spectrum disorders; genetic basis; inflammatory demyelinating disease; genes

Online: 12 May 2023 (11:23:13 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0891.v1

The Impact of the Association Between Structural Changes in Glaucoma as a Primary Element in Visual Perception and Audi-Tory Function on the Diagnostic Management of Glaucomatous Disease

Alina Mihaela Neacsu¹´², Nicoleta Anton³, Lucian Lapusneanu², Valentina Stoian², Maria Cristina Andrei², Mihaela Cosman², Dumitru Ferechide²

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: hearing loss; pure tone audiometry; structural changes in the optic nerve; RNFL; C/D ratio

Online: 12 May 2023 (05:18:02 CEST)

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Background. In the last decade, it was concluded that glaucomatous optic neuropathy is part of the neurodegenerative diseases in which destructive neuronal lesions are located not only in the structure of the retina, but they are also present at the level of the central visual and nervous pathways. Patients with Primitive Open Angle Glaucoma may have experienced changes such as sensorineural hearing loss as well as balance changes. The purpose of this study is to evaluate the degree of involvement of the auditory system in patients with glaucoma, the structural changes in the optic nerve and, to establish correlation between the hearing loss and structural changes in the optic nerve. The subjects included in the study are grouped as follows: a group of patients with glaucoma that will be compared to a group of patients without glaucoma only as well as identi-fy-ing the evolution of structural changes in optic nerve to patients with glaucoma and to normal patients. Material and methods. It is a prospective, cross-sectional study on 32 eyes of 16 subjects with Primitive Open Angle Glaucoma in a study group and 24 eyes of 12 healthy subjects in con-trol group with a mean age of 62 years in both groups. Both groups underwent ophthalmo-logical, audiological and radio imaging evaluation: Pure-tone audiometry (PTA) were recorded, oph-thalmologic evaluations according to a standardized protocol and MRI cerebral examination was performed. Results: In the Study group patients, compared to the Control group, the average lev-els of the left PTA, the cup/disc (C/D) area in both eyes, the C/D ratio in both eyes are in-creased. The mean level of Retinal nerve fiber layer (RNFL) mean thickness was slightly lower in patients with glaucoma. Multivariate analysis demonstrates that gender can be a good predictor of C/D area, gender and age can be good predictors of PTA both eyes and C/D ratio in the right eye, and gender, age and background can be good predictors of disc area in the left eye. Conclu-sions: Pa-tients with Primitive Open Angle Glaucoma show changes in audiometry test in correla-tion with ophthalmological parameters demonstrating that the auditory system can be affected in Primitive Open Angle Glaucoma. This study emphasizes the problem of interdisciplinarity in medicine with the aim of ensuring the quality of life of patients with glaucoma. A good collabora-tion between ophthalmologist and otolaryngologist will be very useful for these patients.

Preprint REVIEW | doi:10.20944/preprints202305.0890.v1

The Role of Blood Oxygen Level Dependent Signal Variability in Pediatrics: A Systematic Review

Michael Francesco Dinatolo, Daiana Roxana Pur, Roy Eagleson, Sandrine De Ribaupierre

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: BOLD Signal Variability; Pediatrics; Biomarker; fMRI; Neurodevelopment

Online: 12 May 2023 (05:16:11 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0656.v1

Motor Cortical Correlates of Paired Associative Stimulation Induced Plasticity: A TMS-EEG Study

Matteo Costanzo, Giorgio Leodori, Carolina Cutrona, Francesco Marchet, Maria Ilenia De Bartolo, Marco Mancuso, Daniele Belvisi, Antonella Conte, Alfredo Berardelli, Giovanni Fabbrini

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: transcranial magnetic stimulation; paired associative stimulation; PAS; cortical plasticity; cortical correlates; TMS-EEG; TMS-Evoked potentials; TEPs; sensorimotor integration

Online: 9 May 2023 (12:47:48 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202305.0595.v1

Osmotic Demyelinataion Syndrome in a Patient With Hyper-Ammonemia and Hyperbilirubinemia: A Case Report and Re-view of the Literature

Kunwoo Park, Sang Beom Kim, Sung Sang Yoon, Ho Geol Woo

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: osmotic demyelination syndrome; hyperammonemia; hyperbilirubinemia

Online: 9 May 2023 (08:16:51 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0375.v1

Clinical Symptoms Influencing Parkinson’s Patients’ Quality of Life in Latvia: A Single-Center Cohort Study

Olga Minibajeva, Estere Zeltiņa, Guntis Karelis, Nataļja Kurjāne, Viktorija Ķēniņa

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Parkinson’s disease; clinical phenotypes; non-motor symptoms; quality of life

Online: 6 May 2023 (04:37:34 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0214.v1

Low-Field Magnetic Stimulation Alleviates MPTP Intoxicated Alterations on Motor Function and Dopaminergic Neurons in Male Mice

Sathiya Sekar, Yanbo Zhang, Hajar Miranzadeh Mahabadi, Benson Buettner, Changiz Taghibiglou

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: MPTP; LFMS; neurons-glial functions; motor function; Parkinson’s disease

Online: 4 May 2023 (07:40:20 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202305.0182.v1

Infantile Hypoxic Encephalopathy with Biphasic Seizures Mimicking Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion (AESD)

Shuhei Fujino, Mikako Enokizono, Tatsuo Kono, Sahoko Miyama

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: acute encephalopathy with biphasic seizures and late reduced diffusion; hypoxic encephalopathy; bright tree appearance; glutamate excitotoxicity; nonconvulsive status epilepticus

Online: 4 May 2023 (04:15:17 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0088.v1

Calcitonin Gene-related Peptide mRNA Synthesis in Trigeminal Ganglion Neurons after Cortical Spreading Depolarization

Mamoru Shibata, Satoshi Kitagawa, Miyuki Unekawa, Tsubasa Takizawa, Jin Nakahara

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: migraine; cortical spreading deapression; calcitonin gene-related peptide (CGRP); trigeminal ganglion; in situ hybridization

Online: 3 May 2023 (02:31:59 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202305.0064.v1

Sleep Links Hippocampal Propensity for Epileptiform Activity to Its Viscerosensory Inputs

Ekaterina Levichkina, Ivan N. Pigarev, David B. Grayden, Steven Petrou, Trichur R Vidyasagar

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: VNS; temporal lobe epilepsy; vagus nerve; interoception; hippocampus; medial septum

Online: 2 May 2023 (07:05:43 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.0025.v1

Beyond the Microbiota: Understanding the Role of the Enteric Nervous System in Parkinson’s Disease From Mice to Human

Martina Montanari, Paola Imbriani, Paola Bonsi, Giuseppina Martella, Antonella Peppe

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Parkinson's Disease; translational medicine; gut-brain axis; enteric nervous system; microbiota; rodent models; clinical evidence

Online: 1 May 2023 (11:04:20 CEST)

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The enteric nervous system (ENS) is a neural network referred to as "the brain in the gut" because of its similarities to the central nervous system (CNS). The ENS consists of numerous types of neurons and glial cells distributed in two intramuscular plexuses that span the length of the intestine and control coordinated smooth muscle contractile activity and other intestinal functions. It is well-established that reciprocal communication exists between the brain and the gastrointestinal tract. Although the ENS can function independently, it is connected to the CNS through the afferent and efferent pathways of the parasympathetic and sympathetic nervous systems. In addition to regulating ENS function by the CNS, these connections are likely to be critically involved in the pathophysiology of Parkinson's disease (PD). PD is a common neurodegenerative disorder that presents with non-motor and motor symptoms. Surprisingly, ENS lesions have been shown to occur very early in the disease, even before CNS involvement. This has led to the postulation that the ENS may be central to the pathophysiology of PD. Autopsy studies have shown that α-synuclein (αS) aggregates in PD patients are found both in the substantia nigra (SN) and the ENS. Therefore, it has been hypothesized that the pathological process leading to PD may initially occur in the ENS years before the appearance of motor features. This process induces misfolding and aggregation of αS in specific subtypes of neurons in the CNS. Finally, it spreads retrogradely in the CNS through preganglionic vagal fibers to the dorsal motor nucleus of this nerve and to other central nervous structures. In addition to the presumed role in the spread of the disease process, it has also been suggested that pathological changes in the ENS might be involved in the gastrointestinal dysfunction frequently seen in Pd patients. Starting from the evidence in animal models and using a translational point of view, in this review, we aim to summarize the role of the ENS in the pathogenesis of PD and how this system could be modulated for a novel therapeutic approach. While acknowledging the presumed role of the microbiome in the gut-brain axis, we will shift the focus from this point of view to focus more on the neurons of the ENS.

Preprint COMMUNICATION | doi:10.20944/preprints202304.1153.v1

Long-Term Pioglitazone Treatment Has No Significant Impact on Microglial Activation and Tau Pathology in P301S Mice

Lea Helena Kunze, François Ruch, Gloria Biechele, Florian Eckenweber, Karin Wind-Mark, Lina Dinkel, Paul Feyen, Peter Bartenstein, Sibylle Ziegler, Lars Paeger, Sabina Tahirovic, Jochen Herms, Matthias Brendel

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: microglia; pioglitazone; TSPO-PET

Online: 28 April 2023 (08:56:28 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.1143.v1

Locus Coeruleus Integrity Is Associated with Higher Openness to Experience and IQ: Implications for the Noradrenergic System for Novelty Seeking in Daily Life

Emanuele Plini, Ian Robertson, Meadhbh Brosnan, Paul Dockree

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Locus Coeruleus; Personality; Openness to Experience; Intelligence

Online: 28 April 2023 (08:16:32 CEST)

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It has been proposed that upregulation of the noradrenergic (NA) system through exposure to novelty might be one of the key components for building cognitive reserve and resilience to neurodegeneration. A personality trait that promotes greater interest in novel experiences is Openness to Experience (OE). Individuals who are high in OE exhibit strong curiosity towards novelty and are more likely to be exposed to novel stimuli throughout the lifespan.Performing voxel-based morphometry analyses, we examined whether OE in 135 healthy young adults was associated with Locus Coeruleus (LC) - the main core of the noradrenergic system. We also investigated whether LC mediates the relationship between OE and a key measure of reserve, I.Q. In comparison with other neuromodulators’ seeds (Dorsal and Median Raphe [DR-MR] -5-HT, Ventral Tegmental Area [VTA] -DA- and Nucleus Basalis of Meynert [NBM] -Ach-), results show that greater LC integrity was related to greater OE and IQ. Additionally, mediation analyses revealed that only LC mediated the relationship between OE and IQ. Furthermore, a Bayesian multiple regression was conducted to model the contribution of both isolated and combined neuromodulator seeds to OE trait express. This approach found that the LC + VTA could account for more variance in OE expression compared to the LC alone. Other weaker but significant associations were observed between DR and OE, between LC + NBM and Conscientiousness and between DR + NBM and Extraversion. These results are together suggestive that OE is primarily underpinned by monoaminergic functioning, and that the LC-NA system plays a central role mediating the interdependence between OE expression and cognition (IQ level). While offering further understanding of the neurobiology of human personality, these findings indicate a pivotal role of LC-NA system integrity in novelty seeking in daily life. This provides a psychobiological account for how OE expression may be beneficial for maintaining the noradrenergic system to facilitate cognitive reserve and resilience to neurodegenerative conditions.

Preprint REVIEW | doi:10.20944/preprints202304.0990.v1

MicroRNAs Role in Diagnosis and Treatment of Subarachnoid Hemorrhage

Zahra Hasanpour Segherlou, Lennon Saldarriga, Esaan Azizi, Kim-Anh Vo, Ramya Reddy, Mohammad Reza Hosseini Siyanaki, Brandon Lucke-Wold

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Aneurysmal Subarachnoid Hemorrhage; microRNAs; Exosomes

Online: 26 April 2023 (12:44:56 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0754.v1

Intracerebral Hematomas are Capable of Altering Air-Pouch Intracranial Pressure Monitoring

Sae-Yeon Won, Sascha Herrmann, Daniel Dubinski, Bedjan Behmanesh, Svorad Trnovec, Nazife Dinc, Joshua Bernstock, Thomas Freiman

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: intracranial pressure (ICP) monitoring; probe placement; air-pouch balloon-assisted probe

Online: 23 April 2023 (03:57:28 CEST)

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Background: Air-pouch balloon-assisted probes have proven to be both simple and reliable tools for intracranial pressure (ICP) monitoring. However, we experienced reproducible falsely high ICP measurement when the ICP probe was inserted in the intracerebral hematoma cavity. Thus, the aim of the experimental and translational study was to analyze the influence of ICP probe placement with regard to measured ICP values. Methods: Two Spiegelberg 3PN-sensors were simultaneously inserted into a closed drain system and were connected to two separate ICP monitors thereby allowing for simultaneous ICP measurements. This closed system was also engineered to allow for pressure to be gradually increased in a controlled fashion. Once the pressure was verified using two identical ICP probes, one of the probes was coated with blood in an effort to replicate placement within an intraparenchymal hematoma. Pressures recorded using the coated probe and control probe were then recorded and compared across a range of 0-60 mmHg. In an effort to further the translational relevance of our results two ICP probes were inserted in a patient that presented with a large basal ganglia hemorrhage that met criteria for ICP monitoring. One probe was inserted into the hematoma and the other into brain parenchyma; ICP values were recorded from both probes and the results compared. Results: The experimental set-up demonstrated a reliable correlation between both control ICP probes. Interestingly, the ICP probe covered with clot displayed a significantly higher average ICP value when compared to the control probe between 0mmHg and 50mmHg (p<0.001); at 60mmHg there was no significant difference noted. Critically, this trend in discordance was even more pronounced in the clinical setting with the ICP probe placed within the hematoma cavity having reported significantly higher ICP values as compared to the probe within brain parenchyma. Conclusion: Our experimental study and clinical pilot highlight a potential pitfall in ICP measurement that may result secondary to probe placement within hematoma. Such aberrant results may lead to inappropriate interventions in an effort to falsely addresses falsely elevated ICPs.

Preprint HYPOTHESIS | doi:10.20944/preprints202303.0476.v2

An Alternative View of Familial Alzheimer’s Disease Genetics

Michael Lardelli

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Alzheimer's Disease; Familial Alzheimer Disease (FAD); presenilins; Amyloid beta Precursor Protein; mutation

Online: 23 April 2023 (02:50:35 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0608.v1

Lower Delayed but Comparable Working Memory Performance in Patients With Parkinson’s Disease

Eun-Young Lee

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: visuospatial working memory; delayed memory; Parkinson’s disease; attentional filtering; lower memory storage

Online: 20 April 2023 (05:27:32 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.0492.v1

Targeting Nociceptors and Transient Receptor Potential Channels for the Treatment of Migraine

Cinder Faith Cohen, Jueun Roh, Sang Hoon Lee, Chul-Kyu Park, Temugin Berta

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: migraine; headache; peripheral sensory neurons; transient receptor potential channels; TRPC4; CGRP

Online: 18 April 2023 (05:23:02 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0405.v1

Diagnostic Effectiveness of [123I]Ioflupane Single Photon Emission Computed Tomography (SPECT) in Multiple System Atrophy

Javier Villena-Salinas, Simeón José Ortega-Lozano, Tomader Amrani-Raissouni, Eduardo Agüera, Javier Caballero-Villarraso

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: multiple system atrophy; dysautonomia; functional neuroimaging testing; diagnostic accuracy; Ioflupane-123; cross-sectional study

Online: 17 April 2023 (04:58:29 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0237.v1

Cognitive Screening in Older People Using Free-Cog and Mini-Addenbrooke’s Cognitive Examination (MACE)

Andrew J. Larner

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: cognitive screening; Efficiency Index; Free-Cog; Mini-Addenbrooke’s Cognitive Examination (MACE); older adults

Online: 12 April 2023 (04:04:12 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.0139.v1

Impacts of Secondhand Smoke on the Onset and Progression of Multiple Sclerosis: A Systematic Review

Marco Antônio Machado Schlindwein, Marcelo Henrique De Moura Campos, Leticia Caroline Breis, Beatriz Sordi Chara, Clara Sasse Scherer, Vitória Augusta Piva Caminski, André Palma Da Cunha Matta, Marcus Vinicius Magno Gonçalves

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Multiple Sclerosis; Onset; Progression; Secondhand Smoke; Systematic Review

Online: 10 April 2023 (04:05:31 CEST)

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Preprint CONCEPT PAPER | doi:10.20944/preprints202304.0108.v1

Towards a Biological Definition of Parkinson’s Disease

Günter U. Höglinger, Charles H. Adler, Daniela Berg, Christine Klein, Tiago F. Outeiro, Werner Poewe, Ronald Postuma, Jon Stoessl, Anthony E. Lang

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Parkinson’s disease; genetics; α-synuclein; neurodegeneration; clinical manifestation; diagnosis

Online: 7 April 2023 (03:54:11 CEST)

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With the growing hope that disease-modifying treatments could target the molecular basis of neurodegenerative diseases even before the onset of symptoms, there is mounting pressure to define disease entities based on pathophysiology rather than on clinical syndromes. The Alzheimer’s disease research community has recently transitioned from diagnostic criteria based on an amnestic syndrome to a purely biomarker-based disease definition, relying on the demonstration of amyloid-beta pathology, tau pathology, and neurodegeneration. In contrast, current diagnostic criteria for Parkinson’s disease still rely on the presence of the well-described clinical syndrome of parkinsonism, with the addition of characteristic motor- and non-motor signs and symptoms. However, there is now unequivocal evidence that Parkinson’s disease starts years before the onset of parkinsonism. Furthermore, neuropathologically defined Lewy body disease is clinically heterogeneous, combining a range of motor, non-motor, dopaminergic and non-dopaminergic features. Finally, clinically defined Parkinson’s disease has diverse underlying etiologies most, but not all, associated with α-synuclein positive Lewy pathology. In light of recent scientific advances, we propose a biologically based definition for the diagnosis of Parkinson's disease, initially to be used for research purposes. The criteria use a three-component ‘G-S-N’ system. The first is documentation of defined gene variants (‘G’), which cause or strongly predispose to PD as the most upstream component. The second is α-synuclein pathology (‘S’), currently defined as pathological α-synuclein deposition in tissue or positive α-synuclein seeding assays. The third is evidence of underlying neurodegeneration (‘N’), currently defined by specific neuroimaging procedures. The associated clinical syndrome (‘C’) is defined by a single high-specificity feature or multiple lower-specificity features. Initiating this transition will enable the field to fuel both basic and clinical research and move closer to the precision medicine required to develop clinically meaningful disease-modifying therapies. We acknowledge current limitations, ethical implications, and the need for prospective validation of this approach.

Preprint REVIEW | doi:10.20944/preprints202304.0098.v1

Therapeutic Potential of Heterocyclic Compounds Targeting Mitochondrial Calcium Homeostasis and Signaling in Alzheimer’s Disease and Parkinson’s Disease

Victor Tapias, Paula González-Andrés, Laura F. Peña, Asunción Barbero, Lucía Núñez, Carlos Villalobos

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Alzheimer’s disease; Parkinson’s disease; mitochondria; oxidative stress; calcium; heterocyclic compounds

Online: 6 April 2023 (13:16:49 CEST)

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The brain is a complex organ that controls body functions and homeostasis through the action of neuronal and glial cells. Neuronal activity is highly energy-dependent and requires large numbers of functional mitochondria to provide substantial amount of energy via mitochondrial oxidative phosphorylation (OXPHOS), the most efficient metabolic process to generate adenosine triphosphate (ATP). Under stress conditions, neurons are particularly vulnerable to mitochondrial dysfunction, leading to decreased ATP synthesis, excessive generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), and intracellular Ca2+ dyshomeostasis, although not necessarily in this order. Alzheimer's disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative diseases in elderly and are characterized by the presence of abnormal protein aggregates and the progressive and irreversible loss of neurons in specific brain regions. The exact mechanisms underlying the etiopathogenesis of AD or PD remain unknown, but there is extensive evidence indicating that compromised mitochondrial energy metabolism along with a depleted antioxidant system play a vital role in the pathophysiology of these neurological disorders. Toxic accumulation of proteins such as amyloid β peptides (Aβ) or amyloid precursor protein (APP) in AD and α-synuclein (α-syn) or leucine-rich repeat kinase 2 (LRRK2) in PD cause mitochondrial deficits through direct inhibition of electron transport chain (ETC) assembly and function, thereby resulting in further generation of ROS/RNS and disturbance of Ca2+ influx. Due to the improvement in life expectancy, the incidence of age-related neurodegenerative diseases has significantly increased. There is no effective protective treatment or therapy available but rather only very limited palliative treatment. There is an urgent need for the development of preventive strategies and disease-modifying therapies (both neuroprotective and neurorestorative interventions) to treat AD/PD. Here, we review the capability of some heterocyclic compounds to modulate Ca2+ homeostasis and signaling with a potential role in regulating mitochondrial function and associated free radical production during the development and onset of AD or PD. Moreover, we have included the chemical synthesis of a series of heterocycles and their derivatives.

Preprint REVIEW | doi:10.20944/preprints202304.0094.v1

SUMOtherapeutics for Ischemic Stroke

Paramesh Karandikar, Jakob Gerstl, Ari Kappel, Sae-Yeon Won, Daniel Dubinski, Monica Emili Garcia-Segura, Florian Gessler, Alfred Pokmeng See, Luca Peruzzotti Jametti, Joshua Bernstock

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: stroke; ischemia; neuroprotection; SUMOylation; experimental therapeutics

Online: 6 April 2023 (12:21:33 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0050.v1

Efficiency Index for Binary Classifiers: Concept, Extension, and Application

Andrew J Larner

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: binary classification; efficiency index

Online: 4 April 2023 (14:39:49 CEST)

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Preprint REVIEW | doi:10.20944/preprints202303.0552.v1

Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step Towards Understanding and Treating Mucopolysaccharidoses

Sofia Carvalho, Juliana Inês Santos, Luciana Moreira, Mariana Gonçalves, Hugo David, Liliana Matos, Marisa Encarnação, Sandra Alves, Maria Francisca Coutinho

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Mucopolysaccharidoses; Disease Modeling; in vitro models; induced Pluripotent Stem Cells (iPSCs); Dental Pulp Stem Cells (DPSC)

Online: 31 March 2023 (14:43:34 CEST)

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Despite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of Mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders, even though the neurological symptoms are currently incurable, even in the cases where a dis-ease-specific therapeutic approach does exist. One of the best ways to get insights on the molecular mechanisms driving that pathogenesis is the analysis of patient-derived cells. Yet, not every pa-tient-derived cell holds potential to recapitulate relevant disease features. For the neurodegenerative forms of these diseases in particular, it is challenging to grow neuronal cultures that accurately represent them because of the obvious inability to access live neurons. This scenario changed sig-nificantly since Yamanaka et al. published their protocol for induction of pluripotent stem cells (SC) from adult human fibroblasts. From then on, a series of differentiation protocols to generate neurons from induced pluripotent stem cells (iPSC) was developed and extensively used for disease mod-eling. Currently, human iPSC and iPSC-derived cell models have been generated for several MPS and numerous lessons were learnt from their analysis. Here we review most of those studies, not only listing the currently available MPS iPSC lines and their derived models, but also summarizing how they were generated and the major information different groups have gathered from their analysis. Finally, and taking into account that iPSC generation is a laborious/expensive protocol that holds significant limitations, we also comment on a tempting alternative to establish MPS pa-tient-derived neuronal cells in a much more expedite way by taking advantage of the existence of a population of multipotent SC in human dental pulp, to establish mixed neuronal and glial cultures.

Preprint COMMUNICATION | doi:10.20944/preprints202303.0542.v1

Central Nervous System Source Modulates Microglia Function and Morphology In Vitro

Andreia G Pinho, Andreia Monteiro, Sara Fernandes, Nídia De Sousa, António Salgado, Nuno A. Silva, Susana Monteiro

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: microglia; cortex; spinal cord; morphology; phagocytosis; in vitro studies

Online: 31 March 2023 (04:09:06 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202303.0525.v1

LPS-Induced Systemic Inflammation Affects the Dynamic Interactions of Astrocytes and Microglia with the Vasculature of the Mouse Brain Cortex

Evangelia Xingi, Paraskevi N. N Koutsoudaki, Irini Thanou, Minh-Son Phan, Maria Margariti, Anja Scheller, Jean-Yves Tinevez, Frank Kirchhoff, Dimitra Thomaidou

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: astrocytes; microglia; 2-photon imaging; NVU; LPS; blood vessels; AQP4

Online: 30 March 2023 (10:06:21 CEST)

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Preprint REVIEW | doi:10.20944/preprints202303.0484.v1

Mitochondrial Bioenergy in Neural Disease: Huntington and Parkinson

Annalisa Tassone, Maria Meringolo, Giulia Ponterio, Paola Bonsi, Tommaso Schirinzi, Giuseppina Martella

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: movement disorders; mitochondria; energy metabolism; synaptic plasticity; basal ganglia; calcium

Online: 28 March 2023 (10:23:10 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202303.0476.v1

An Alternative View of Familial Alzheimer’s Disease Genetics

Michael Lardelli

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Alzheimer's Disease; Familial Alzheimer Disease (FAD); presenilins; Amyloid beta Precursor Protein; mutation

Online: 28 March 2023 (08:24:53 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202303.0017.v1

Characteristics of Sleep and Autonomic Activity in Active Older Adults Based on Metabolic Age: A Case Report

Miki Sato, Ryuichi Tanioka, Feni Betriana, Kyoko Osaka, Yueren Zhao, Tetsuya Tanioka, Akira Takahashi

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: healthy aging; autonomic nervous activities; heart rate variability; sleep status; well-being

Online: 1 March 2023 (09:12:46 CET)

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Preprint REVIEW | doi:10.20944/preprints202302.0471.v1

Multi-mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Daniel G Lynch, Raj K Narayan, Chunyan Li

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Traumatic brain injury; Combination therapy; Multimodal therapy; Multimodal neuromonitoring; Pharmacologic; Non-pharmacologic

Online: 27 February 2023 (10:10:08 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0461.v1

The Case For Including Neuroprotective Factors in Sporadic Creutzfeldt-Jakob Questionnaires

Robert Reed

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Prion Disease; Creutzfeldt-Jakob; Diet; Dementia

Online: 27 February 2023 (08:42:14 CET)

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Preprint CONCEPT PAPER | doi:10.20944/preprints202302.0421.v1

Home-Based Moderate Intensity Cycling in Community Dwelling Individuals With Stroke: Protocol of a Randomised Controlled Study

Mats van Mechelen, Dennis Lemmens, Christel Vanroy, Steven Truijen, Wim Saeys

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: stroke; aerobic exercise; cycling; moderate intensity; home-based

Online: 24 February 2023 (08:50:13 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0411.v1

Role of Perfusion Tomography in Traumatic Acute Subdural Hematoma: A Pilot Study

Robson Amorim, Vinicius Trindade Silva, Henrique Oliveira Martins, Sérgio Brasil, Daniel Godoy, Matheus Teixeira Mendes, Gabriel Gattas, Edson Bor-Seng-Shu, Wellingson Paiva

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Acute subdural hematomas; traumatic brain injury; computed tomography perfusion; cerebral hemodynamics

Online: 23 February 2023 (15:34:27 CET)

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Preprint REVIEW | doi:10.20944/preprints202302.0295.v1

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Stefanie Schreiber, Jose Bernal, Philipp Ulbrich, Frank Schreiber, Patrick Müller, Rüdiger Christian Braun-Dullaeus, Maria Del Carmen Valdés-Hernándes, Roberto Duarte, Joanna Marguerite Wardlaw, Sven Günther Meuth, Grazia Mietzner, Stefan Vielhaber, Alexander Dityatev, Solveig Jandke, Hendrik Mattern

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: amyotrophic lateral sclerosis; vascular supply; motor cortex; pericytes; exerkines

Online: 17 February 2023 (04:47:49 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0044.v1

Qualitative Evaluation of Intracranial Pressure Slopes in Patients Undergoing Brain Death Protocol

Mylena Miki Ideta, Louise Makarem Oliveira, Daniel Buzaglo Gonçalves, Mylla Christie Paschoalino, Nise Alessandra Carvalho, Marcus Vinicius Della Coletta, Wellingson Paiva, Sérgio Brasil, Robson L. O. Amorim

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Brain death diagnosis; Intracranial Pressure; Intracranial compliance

Online: 2 February 2023 (11:30:01 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202301.0469.v1

Fremanezumab and Non-High-Dose Galcanezumab for Comorbid Cluster Headache in Patients With Migraine: 3 Cases

Kenta Kashiwagi, Masahito Katsuki, Shin Kawamura, Senju Tachikawa, Atsuko Ono, Akihito Koh

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: anti-calcitonin gene-related peptide monoclonal antibodies; cluster headache; migraine; real-world; galcanezumab; fremanezumab; comorbidity

Online: 26 January 2023 (04:24:39 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0297.v3

Insulin in Amyotrophic Lateral Sclerosis: Impairment, Tests and Treatment

Ari Rappoport

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: ALS; frontotemporal dementia; insulin; diabetes

Online: 24 January 2023 (10:25:55 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202301.0379.v1

Combined Invasive Peripheral Nerve Stimulation in the Management of Chronic Post-Intracranial Disorder Headache. A Case Report.

Athanasia Alexoudi, Eustathios Vlahakis, Stamatios Banos, Konstantinos Oikonomou, Panayiotis Patrikelis, Anastasia Verentzioti, Maria Stefanatou, Stylianos Gatzonis, Stefanos Korfias, Damianos Sakas

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Combined Peripheral Nerve Stimulation; occipital nerve stimulation; secondary headache disor-ders; chronic post-intracranial disorder headache and case report

Online: 23 January 2023 (00:57:59 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0375.v1

The Role of Mu Opioid Receptors in High Fat Diet-induced Reward and Potentiation of the Rewarding Effect of Oxycodone

Asif Iqbal, Abdul Hamid, Syed Muzzammil Ahmad, Kabirullah Lutfy

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: High fat diet; conditioned place preference; mu opioid receptor; knockout mice; wildtype mice; endogenous opioid system; oxycodone.

Online: 22 January 2023 (03:51:26 CET)

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Excessive high fat diet (HFD) consumption can induce food addiction which is believed to involve the communication between the hypothalamus and mesolimbic dopaminergic neurons, originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc). These brain regions are densely populated with opioid receptors, raising the possibility that these receptors, and particularly mu opioid receptors (MORs), are involved in mediating reward induced by palatable foods. This study sought to investigate the involvement of MORs in high fat diet (HFD)-induced reward and if there is any difference between male and female subjects in this response. We also assessed if exposure to HFD would potentiate the rewarding action of oxycodone, a relatively selective MOR agonist. The place conditioning paradigm was used to determine if conditioning for a short time (STC, 2 h) or long time (LTC, 16 h) with HFD induces reward or alters the rewarding action of oxycodone. Male and female C57BL/6J mice as well as MOR knockout and wildtype mice of both sexes were tested for basal place preference on day 1 and then conditioned with HFD in one chamber and regular chow diet (RCD) in another chamber and tested for place preference again after three sets of STC and again after a set of LTC. Each set consisted of two conditioning with RCD and two conditioning with HFD. Controls were conditioned with RCD in both conditioning chambers. Following the last place preference test, mice were treated with oxycodone and conditioned in the HFD-paired chamber and saline in the RCD-paired chamber for one hour once a day to explore the possibility if the HFD could alter oxycodone reward. The result showed that HFD induced conditioned place preference (CPP) in both male and female subjects following the LTC. This response was further potentiated after oxycodone conditioning. The latter response was mediated via MORs, as it was blunted in MOR knockout mice. However, HFD-induced CPP was observed following LTC in only female MOR knockout mice, suggesting for sexual dimorphism in this response.

Preprint REVIEW | doi:10.20944/preprints202301.0220.v1

Multiple System Atrophy : Mitochondria Dysregulation, Reprogramming and Alternative of Neuroprotective Agents

Sri Widyarti, Syahputra Wibowo, Akhmad Sabarudin, Intan Abhirama, Sutiman Bambang Sumitro

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Hydrogen, Mitochondrial Dysregulation, MSA, Multiple System Atrophy

Online: 12 January 2023 (09:06:18 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0079.v1

The Role of CHI3L1 Plasmatic Levels in Amyotrophic Lateral Sclerosis

Alessandro Bombaci, Umberto Manera, Giovanni De Marco, Federico Casale, Paolina Salamone, Giuseppe Fuda, Giulia Marchese, Barbara Iazzolino, Laura Peotta, Cristina Moglia, Andrea Calvo, Adriano Chiò

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: ALS; HSP; chitinases; biomarker; differential diagnosis; early diagnosis; cognitive impairment; MND mimics; red blood cells; haemoglobin

Online: 4 January 2023 (11:02:27 CET)

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Preprint REVIEW | doi:10.20944/preprints202301.0034.v1

Exploring Novel Therapeutic Targets in the Common Pathogenic Factors in Migraine and Neuropathic Pain

János Tajti, Délia Szok, Anett Csáti, Ágnes Szabó, Masaru Tanaka, And László Vécsei

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: migraine; neuropathic pain; calcitonin gene-related peptide (CGRP); kynurenine; glia; cytokines; neuroinflammation; transient receptor potential (TRP) ion channels; endocannabinoids

Online: 4 January 2023 (01:53:45 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0001.v1

Bright Morning Light Enhances Parasympathetic Activity at Night: A Pilot Study of Older People with Dementia, without a Pacemaker

Chuen-Ru Liu, Terry B. J. Kuo, Jwo-Huei Jou, Chun-Ting Lai Lai, Yu-Kai Chang, Yiing Mei Liou

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: light therapy; dementia; heart rate variability; cognitive function; parasympathetic; sympathetic

Online: 3 January 2023 (02:27:06 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0452.v1

Idiopathic Normal Pressure Hydrocephalus Diagnosis: Quantitative and Qualitative Score Predicting Outcome of Extended Lumbar Drainage

Maria Caffo, Roberta Laera, Maria Luisa Gorgoglione, Antonello Curcio, Giuseppina Marzano, Gerardo Caruso, Antonino Germanò

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Extended lumbar drainage; Hydrocephalus; Idiopathic normal pressure hydrocephalus; neurodegenerative diseases; Qualitative neurocognitive tests; Quantitative neurocognitive tests

Online: 23 December 2022 (08:09:41 CET)

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Background: Idiopathic normal pressure hydrocephalus is a syndrome with neuroradiological findings and clinical pattern characteristic but not specific for the pathology. Since the prevalence is growing due to the rapidly aging society, standardized and validated protocol for diagnosis is needed, also because this condition may mimic other disorders among elderly such as Parkinson's and Alzheimer's disease. Material and methods: We analysed data from 44 patients with suspect diagnosis of idiopathic normal pressure hydrocephalus with age > 60 years, clinical triad and neuroradiological pattern examined in our ward from November 2018 to November 2022. Neu-ropsychological assessment includes Mini Mental State Examination and Mental Deterioration Battery. Motor scores were collected from gait and balance tests. The evaluation was performed before and after an extended lumbar drainage last 48h. Patients who has scores improvement after the extended lumbar drainage, undergo ventriculoperitoneal shunt with a programmable valve. Results: All patients undergo neuropsychological assessment and motor tests, only 2 patients were unable to perform motor tests because bedridden. 16 patients showed no benefit from the tests, in 2 cases even a worsening of cognitive performance. 28 patients showed an improvement in their performances, but in most cases the improvement involved only the neuropsychological as-sessment. All patients underwent ventriculoperitoneal shunt have had a typical answers pattern in Mental Deterioration Battery test. We performed 9 ventriculoperitoneal shunt and 1 ventricu-lo-atrial shunt. Conclusions: Qualitative neurocognitive tests come out to be more sensitive compared to quantitative neurocognitive tests in identifying patients with suspected idiopathic normal pressure hydrocephalus benefiting from extended lumbar drainage test and then un-derwent surgical treatment. This could be considered a valid screening in elderly patients with suspected idiopathic normal pressure hydrocephalus in order to minimize the number of invasive procedures. More studies are necessary to validate this tool.

Preprint ARTICLE | doi:10.20944/preprints202212.0297.v2

Insulin-Based Treatment for Amyotrophic Lateral Sclerosis

Ari Rappoport

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: ALS; frontotemporal dementia; insulin; diabetes

Online: 20 December 2022 (08:49:21 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0297.v1

Insulin-Based Treatment for Amyotrophic Lateral Sclerosis

Ari Rappoport

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: ALS; frontotemporal dementia; insulin; diabetes

Online: 16 December 2022 (08:04:09 CET)

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Preprint REVIEW | doi:10.20944/preprints202212.0222.v1

The Entity of Cerebellar Mutism Syndrome: A Narrative Review Centered on the Etiology, Diagnostics, Prevention, and Therapeutic Options

DIMITRIOS PANAGOPOULOS, GEORGIOS STRANJALIS, Maro Gavra, Efstathios Boviatsis, Stefanos Korfias, Ploutarchos Karydakis, Marios Tmemistocleous

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: cerebellal mutism syndrome,; cerebello-cerebral diaschisis; posterior fossa tumor; vermis language impairment

Online: 13 December 2022 (02:35:01 CET)

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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.

Preprint ARTICLE | doi:10.20944/preprints202212.0089.v1

Evgeny Blagovechtchenski, Maria Koriakina, Dimitri Bredikhin, Olga Agranovich, Dzerassa Kadieva, Evgenia Ermolovich, Iiro P Jääskeläinen, Anna N Shestakova

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Cognitive function; arthrogryposis; obstetrics palsy; children; motor disorder

Online: 6 December 2022 (02:31:36 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0051.v1

AI-based Detection of Aspiration for Video-endoscopy with Visual Aids in Meaningful Frames to Interpret the Model Outcome

Jürgen Konradi, Milla Zajber, Ullrich Betz, Philipp Drees, Annika Gerken, Hans Meine

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: XAI; segmentation; detection; aspiration; glottis; vocal cords; endoscopy; FEES; interpretability; meaningful sequences; key frames

Online: 2 December 2022 (12:22:54 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202212.0041.v1

Fatal Case of Imported Tick-Borne Encephalitis in South Serbia

Lidija Popović Dragonjić, Miodrag Vrbić, Aleksandar Tasić, Verica Simin, Ivana Bogdan, Dragana Mijatović, Alejandro Cabezas-Cruz, Pavle Banović

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: tick-borne encephalitis; tick; Serbia; Switzerland; fatal

Online: 2 December 2022 (07:14:48 CET)

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Preprint REVIEW | doi:10.20944/preprints202211.0447.v1

EEG in Neurorehabilitation can have Several Uses other than BCI: Biomarkers to Predict/Monitor Recovery

Athanasia Tsiamalou, Efthimios Dardiotis, Konstantinos Paterakis, George Fotakopoulos, Ioannis Liampas, Markos Sgantzos, Vasileios Siokas, Alexandros G Brotis

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: EEG; stroke; traumatic brain injury; neurorehabilitation; brain-machine interface

Online: 24 November 2022 (02:08:43 CET)

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Background: There is an increasing interest in the role of EEG in neurorehabilitation. We primarily aimed to identify the knowledge base through highly influential studies. Our secondary aims were to imprint the relevant thematic hotspots, research trends, and social networks within the scientific community. Methods: We performed an electronic search in Scopus looking for studies reporting on rehabilitation in patients with neurological disabilities. The most influential papers outlined the knowledge base, while a word co-occurrence analysis imprinted the research hotspots. Likewise, co-citation analyses highlighted collaboration networks between Universities, authors, and countries. The results were presented in summary tables, burst detection plots, and geospatial maps. Finally, a content review based on the top-20 most cited articles completed our study. Results: Our current bibliometric study was based on 874 records from 420 sources. There was a vivid research interest in EEG use for neurorehabilitation, with an annual growth rate as high as 14.3%. The most influential paper was the study titled "Brain-computer interfaces, a review" by Nicolas-Alfonso LF and Gomez-Gill J, with 997 citations, followed by "Brain-computer interfaces in neurological rehabilitation" by Daly J. and Wolpaw JR (708 citations). The USA, Italy, and Germany were among the most productive countries. The research hotspots shifted with time from the use of “functional magnetic imaging” to EEG-based “brain-machine interface”, “motor imagery”, and “deep learning”. Conclusions: EEG constitutes the most significant input in brain-computer interfaces (BCI) and can be successfully used in the neurorehabilitation of patients with stroke, amyotrophic lateral sclerosis, and traumatic brain and spinal injury. EEG-based BCI facilitates training, communication, and control of wheelchair and exoskeletons. However, research is limited to specific scientific groups from developed countries. Evidence is expected to change with the broader availability of BCI and improvement in EEG filtering algorithms.

Preprint REVIEW | doi:10.20944/preprints202211.0186.v2

Curcumin and Its Affection for Sleep Deprivation

Ramendra Pandey, Rohit Kumar, Chung-Ming Chang

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Sleep deprivation; Cytokines; curcumin; nano – curcumin

Online: 11 November 2022 (02:06:44 CET)

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Preprint REVIEW | doi:10.20944/preprints202211.0186.v1

Curcumin and Its Affection for Sleep Deprivation

Ramendra Pandey, Rohit Kumar

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Sleep deprivation; Cytokines; curcumin; nano – curcumin

Online: 10 November 2022 (03:15:58 CET)

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Preprint REVIEW | doi:10.20944/preprints202211.0177.v1

Monoclonal Antibodies Against Calcitonin Gene-related Peptide for Migraine Prophylaxis: A Systematic Review of Real-world Data

Antun Pavelic, Christian Wöber, Franz Riederer, Karin Zebenholzer

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Real-world; Erenumab; Galcanezumab; Fremanezumab; Eptinezumab; pharmacoepidemiology; effectiveness; tolerability; safety; treatment pause; switching

Online: 9 November 2022 (11:51:21 CET)

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Preprint ARTICLE | doi:10.20944/preprints202211.0171.v1

Whole CNS 3D Cryo-fluorescence Tomography Shows CSF Clearance along Nasal Lymphatics, Spinal Nerves, and Lumbar/Sacral Lymph Nodes

Christian Stokes, Eli F White, Steve Toddes, Nicole Bens, Praveen Kulkarni, CRAIG F FERRIS

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: brain clearance; Qdots; nasal turbinates; subarachnoid space; cervical lymphatics; sympathetic ganglia; cervical spinal cord; thoracic spinal cord

Online: 9 November 2022 (08:57:11 CET)

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Unwanted proteins and metabolic waste in cerebral spinal fluid are cleared from the brain by meningeal and nasal lymphatics, and perineural sheath of cranial nerves; however, the distribution and clearance of CSF along the subarachnoid space of the entire spinal cord is not fully understood. It was hypothesized that the anatomical resolution of Cryo-Fluorescence Tomography (CFT) could provide the visual evidence of clearance across the spinal cord at each level of the vertebral column. To that end, isoflurane anesthetized mice were infused into the lateral cerebroventricle with 5.0 µl of quantum dots [QdotR 605 ITKTM amino (PEG)] over two mins. Mice were allowed to recover (ca 2-3 min) and remained awake and ambulatory for 5, 15, 30, 60 and 120 minutes after which they were euthanized, and the entire intact body frozen at -800. The entire mouse was sectioned and imaged to produce an isotropic voxel resolution of 35 µm. Both white light and fluorescent images were captured after each slice to produce high resolution three-dimensional volumes for each mouse. CFT highlighted the circulation of tracer throughout the ventricular system and central canal of the spinal cord and the entire subarachnoid space of the CNS. Signal could be visualized in the nasal cavity, deep cervical lymph nodes, thoracic lymph nodes and more superficial submandibular lymph nodes as early as 15 min post infusion. Fluorescent signal could be visualized along the dorsal root ganglia and down the proximal extension of the spinal nerves of the thoracic and lumbar segments at 30 min. There was significant accumulation of tracer in the lumbar and sacral lymph nodes between 15- 60 min. The dense fluorescent signal in the thoracic vertebrae noted at 5- and 15-mins post infusion was significantly reduced by 30 min. Indeed, all signal in the spinal cord was ostensibly absent by 120 min except for trace amounts in the coccyx. The brain still had some residual signal at 120 min. These data show that Qdots with a hydrodynamic diameter of 16-20 nm rapidly clear from the brain of awake mice. These data also clearly demonstrate the rapid distribution and efflux of trace along a major length of the vertebral column and the potential contribution of the spinal cord in the clearance of brain waste.

Preprint CASE REPORT | doi:10.20944/preprints202211.0153.v1

Successful Treatment With Minocycline and Saiko-Keishi-to for Covid-19-Associated CNS Lesion

Masashi Ohe, Shida Haruki, Junya Yamamoto, Masahide Seki, Ken Furuya

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: COVID-19; minocycline; saiko-keishi-to

Online: 8 November 2022 (10:28:06 CET)

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Preprint REVIEW | doi:10.20944/preprints202211.0140.v1

The Molecular, Neurological, and Clinical Features of Diffuse Intrinsic Pontine Glioma

Kristen Denniston, Alexandra Dickson, Alexandra Fitzsimmons, Gabrielle Verbeke-O'Boyle, Brian Piper

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Diffuse Intrinsic PontineDiffuse Intrinsic Pontine Glioma; DIPG; pediatric tumors; cancer; CAR-T; pons; histone mutation

Online: 8 November 2022 (02:57:43 CET)

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Preprint REVIEW | doi:10.20944/preprints202211.0042.v1

Machine Learning and Eye Movements Give Insights into Neurodegenerative Disease Mechanisms

Andrzej W. Przybyszewski, Albert Śledzianowski, Artur Chudzik, Stanisław Szlufik, Dariusz Koziorowski

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Alzheimer’s Disease; Parkinson’s Disease; eye movements; Rough Set; Machine Learning

Online: 2 November 2022 (04:12:08 CET)

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Preprint REVIEW | doi:10.20944/preprints202211.0032.v1

Nano-Theranostics Approaches and Mitochondrial Targeted Drug Delivery: Alzheimer ’s Disease Therapeutic Interventions

Leena Chacko, Sagnik Nag, Saikat Dewanjee, Subhrojyoti Ghosh, Jayalakshmi Vallamkondu, Oishi Mitra, Anuvab Dey, Tiyasa Bhuniya, Hari Prasad Reddy Paluru, P. Hemachandra Reddy, Ramesh Kandimalla

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Alzheimer’s disease; Quantum Dot Nanoparticles; PINK1; Theranostic; mitochondria; drug delivery

Online: 1 November 2022 (14:29:26 CET)

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Preprint ARTICLE | doi:10.20944/preprints202210.0384.v1

Marital Status with Rey Auditory Verbal Learning Test Cognition Performance Is Associated with Mild Cognitive Impairment

Yohn Jairo Parra Bautista, Samia Messeha, Carlos Theran, Richard A Alo, Clement G. Yedjou, Victor Adankai, Samuel Babatunde

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Cognitive Test; Education; Cognitive Impairment; Dementia

Online: 25 October 2022 (09:37:41 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202210.0382.v1

Cortical Reorganization of Early Somatosensory Processing in Hemiparetic Stroke

Jordan N Williamson, William A Sikora, Nishaal J Parmar, Louis V Lepak, Carolyn F Cheema, Hazem H Refai, Julius P Dewald, Dee H Wu, Evgeny V Sidorov, Yuan Yang

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Hemiparetic stroke; Cortical Reorganization; Somatosensory Evoked Potentials; EEG; Sensorimotor System.

Online: 25 October 2022 (08:39:11 CEST)

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Preprint REVIEW | doi:10.20944/preprints202210.0359.v1

Plastic Spinal Motor Circuits in Health and Disease

Uwe Windhorst, Payam Dibaj

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Spinal plasticity; spinal neuronal networks; spinal muscular atrophy; amyotrophic lateral sclerosis; spinal cord injury; stroke; spasticity; classical conditioning; instrumental conditioning; operant conditioning

Online: 24 October 2022 (10:05:33 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202210.0250.v1

“Neuro-Fiber Mapping”: An Original Concept of Spinal Cord Neural Network Spatial Targeting using Live Electrostimulation Mapping to (Re)explore the Conus Medullaris Anatomy

Philippe Rigoard, Maarten Moens, Lisa Goudman, Tom Le Tutour, Michel Rochette, Jonathan Dany, Mohamed Et Talby, Manuel Roulaud, Rémi Hervochon, Amine Ounajim, Kévin Nivole, Romain David, Maxime Billot

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: anatomy; neuroanatomy; conus medullaris; Multicolumn Spinal Cord Stimulation (SCS); soma-totopy; dorsal columns; Computerized Electrical Modeling; Neuro-Fiber-Mapping; super-selective spinal cord stimulation

Online: 18 October 2022 (05:29:38 CEST)

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Preprint REVIEW | doi:10.20944/preprints202210.0194.v1

Blood-Brain Barrier Transport of Transferrin-Receptor Targeted Nanoparticles

Maj Schneider Thomsen, Kasper Bendix Johnsen, Krzysztof Kucharz, Martin Lauritzen, Torben Moos

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Antibody; blood-brain barrier; endosomal; liposome; nanoparticle; targeting; transferrin

Online: 13 October 2022 (11:52:50 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202209.0175.v2

A Qualitative Assessment Among Personnel Working In Community-Led Development Programme Settings Regarding Sexualized Substance Use

Binata Marik, Nupur Mahajan, Rohit Sarkar, Rochana Mitra, Rajiv Dua, Sumit Aggarwal

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: sexually transmitted infection (STI); HIV; viral hepatitis; transgender persons; in-depth interviews (IDIs); formative research

Online: 12 October 2022 (14:57:14 CEST)

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Background: Sexualized substance use (SSU) is the practice of psychotropic substance usage, before or during sexual intercourse in order to increase sexual pleasure and arousal. It has a strong association with sexually transmitted infections (STIs). The present study aimed to assess the knowledge gaps regarding SSUs among the community health mobilizers by interviewing them regarding their knowledge, attitudes, and practices through qualitative approach. Methodology: In-depth interviews (IDIs) were conducted with a total of nineteen community health mobilizers engaged in counselling of sexualized substance users. A semi-structured open-ended questionnaire with socio-demographic information and probes related to SSU was administered. Informed consent was taken from each participant prior to data collection. Results: Gender-wise distribution indicated that 47% of the community mobilizers are men, followed by transgender persons (32%), and women (21%). Responses of participants highlighted that alcohol consumption was the most observed form of SSU. The findings indicated that drug administration through injection was most common, followed by sniffing and swallowing. Sources of drug pro-curement enlisted by participants included peddlers, peer groups, sexual parties, medical and liquor stores. Only 63% of participants had fair knowledge about STIs such as HIV, viral hepatitis, syphilis, and gonorrhoea. All were familiar with the administration of naloxone injections and the locations of nearby hospitals where patients could be transported in the event of an overdose. Conclusions: The in-depth interviews among the study participants reflected substantial know-ledge gaps related to various areas associated with SSU, which highlights the need for periodic workshops and training for upgradation of existing knowledge and practices among community health mobilizers. This will help to broaden their knowledge of different types of SSUs, the latest substances of abuse, the diseases caused by high-risk sexual practices, and additional health and psychological issues associated with SSUs, which would ultimately help in better counseling and management of sexualized substance users. It may also play a crucial role in the strengthening of capacity-building systems and engagements at the community level. This study may be used as formative research by researchers and policy makers to develop study protocols for multi-centric community-based studies among community health mobilizers and sexualized substance users across the country for further validation and exploration.

Preprint REVIEW | doi:10.20944/preprints202209.0412.v1

Intertwining Neuropathogenic Impacts of Aberrant Circadian Rhythm and Impaired Neuroregenerative Plasticity in Hutington’s Disease: Neurotherapeutic Significance of Chemogenetics

Sowbarnika Ravichandran, Ramalingam Suhasini, Sudiksha Madheswaran Deepa, Divya Bharathi Selvaraj, Jemi Feiona Vergil Andrews, Viruthachalam Thiagarajan, Mahesh Kandasamy

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Huntington’s disease; circadian rhythm; clock genes; adult neurogenesis; chemogenetics

Online: 27 September 2022 (04:45:35 CEST)

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Preprint REVIEW | doi:10.20944/preprints202209.0327.v1

Bioinformatic Methods for Identifying Differentially Abundant Subpopulations in scRNA-seq Data

Giona Kleinberg, Ashwini Shinde, Sai Batchu, Michael Diaz, Kevin Root, Brandon Lucke-Wold

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: scRNA-seq; bioinformatics; subpopulations; analysis methods; single-cell RNA sequencing

Online: 21 September 2022 (11:22:50 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202209.0287.v1

Anticholinesterase and Pro-dopaminergic Effects of Instant Coffee

Daniele O. Köhn, Graziella R. Molska, Lyvia Izaura G. Paula-Freire, Giuseppina Negri, Elisaldo A. Carlini, Fúlvio R. Mendes

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Coffea arabica; antioxidant; acetylcholinesterase inhibition; catalepsy; unilateral 6-hydroxydopamine lesion; caffeine

Online: 20 September 2022 (03:22:27 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202209.0197.v1

Alpha-Synuclein at the Interface between Depression, Parkinson’s Disease and Dementia: Evidence from Epidemiology, Population Genetics and Gene-Environment Interactions

Ravi Philip Rajkumar

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: alpha-synuclein; SNCA; major depression; dysthymia; Parkinson’s disease; dementia; neurodegeneration; gene-environment interaction; PM2.5; pesticides

Online: 14 September 2022 (08:38:38 CEST)

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Preprint CONCEPT PAPER | doi:10.20944/preprints202205.0281.v2

A Molecular Framework for Autistic Experiences: Mitochondrial Allostatic Load as A Mediator between Autism and Psychopathology

Caitlyn Mahony, Colleen O' Ryan

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: autism; autistic burnout; social camouflaging; early life stress; suicidality; psychopathology; mitochondrial allostatic load

Online: 5 September 2022 (03:35:24 CEST)

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Molecular autism research is evolving towards a biopsychosocial framework that is more informed by autistic experiences. In this context, research aims are moving away from correcting external autistic behaviors and towards alleviating internal distress. Autism Spectrum Conditions (ASCs) are associated with high rates of depression, suicidality and other comorbid psychopathologies, but this relationship is poorly understood. Here, we integrate emerging characterizations of internal autistic experiences within a molecular framework to yield insight into the prevalence of psychopathology in ASC. We demonstrate that descriptions of social camouflaging and autistic burnout resonate closely with the accepted definitions for early life stress (ELS) and chronic adolescent stress (CAS). We propose that social camouflaging could be considered a distinct form of CAS that contributes to allostatic overload, culminating in a pathophysiological state that is experienced as autistic burnout. Autistic burnout is thought to contribute to psychopathology via psychological and physiological mechanisms, but these remain largely unexplored by molecular researchers. Building on converging fields in molecular neuroscience, we discuss the substantial evidence implicating mitochondrial dysfunction in ASC to propose a novel role for mitochondrial allostatic load in the relationship between autism and psychopathology. An interplay between mitochondrial, neuroimmune and neuroendocrine signaling is increasingly implicated in stress-related psychopathologies, and these molecular players are also associated with neurodevelopmental, neurophysiological and neurochemical aspects of ASC etiology. Together, this suggests an increased exposure and underlying molecular susceptibility to ELS that increases the risk of psychopathology in ASC. This article describes an integrative framework shaped by autistic experiences that highlights novel avenues for molecular research into mechanisms that directly affect the quality of life and well-being of autistic individuals. Moreover, this framework emphasizes the need for increased access to diagnoses, accommodations, and resources to improve mental health outcomes in autism.

Preprint ARTICLE | doi:10.20944/preprints202209.0028.v1

The Habits of the Indonesian People by Drinking Coffee with the Incidence of Hypertension

Candra Kusuma Negara, Moses Glorino Rumambo Pandin

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Hypertension; drinking coffee

Online: 2 September 2022 (02:41:17 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202209.0013.v1

The Impact of Highly Effective Treatment in Pediatric-Onset Multiple Sclerosis: A Case-Series

Paolo Immovilli, Paola De Mitri, Veronica Bazzurri, Stefano Vollaro, Nicola Morelli, Giacomo Biasucci, Fabiola Magnifico, Elena Marchesi, Maria Lara Lombardelli, Lorenza Gelati, Donata Guidetti

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: pediatric onset multiple sclerosis; POMS; highly effective treatments; disease modifying drugs; DMD

Online: 1 September 2022 (08:48:04 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202208.0501.v1

Aconitum Alkaloid Songorine Exerts Potent Gamma-aminobutyric Acid A Receptor Agonist Action In Vivo and Effectively Decreases Anxiety Without Adverse Sedative or Psychomotor Effects in the Rat

Zsolt Kristóf Bali, Nóra Bruszt, Zsombor Kőszegi, Lili Veronika Nagy, Tamás Atlasz, Péter Kovács, Dezső Csupor, Boglárka Csupor-Löffler, István Hernádi

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: GABA-A receptors; in vivo electrophysiology; microiontophoresis; vigilance; anxiety; behavioral pharmacology; diterpene alkaloids; picrotoxin; saclofen; songorine

Online: 30 August 2022 (03:45:03 CEST)

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Preprint REVIEW | doi:10.20944/preprints202208.0417.v1

A Review on the Technological Advances and Future Perspectives of Axon Guidance and Regeneration in Peripheral Nerve Repair

Arjun Prasad Tiwari, Taylor Lokai, Bayne Albin, In Hong Yang

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: axon guidance; peripheral nerves regeneration; bioengineering approach; optogenetic stimulation

Online: 24 August 2022 (08:39:01 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202208.0394.v1

Has the Timing of the Surgery a Major Role in Influencing Outcome in Elderly Patients with Acute Subdural Hematomas?

Gianluca Trevisi, Alba Scerrati, Oriela Rustemi, Luca Ricciardi, Tamara Ius, Anna Maria Auricchio, Pasquale De Bonis, Alessio Albanese, Annunziato Mangiola, Rosario Maugeri, Federico Nicolosi, Carmelo Lucio Sturiale

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: acute subdural hematoma; comorbidity; elderly; outcome; surgery; timing of surgery; traumatic brain injury

Online: 23 August 2022 (05:08:46 CEST)

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Preprint REVIEW | doi:10.20944/preprints202208.0190.v1

Neurovascular Manifestations of Iron-Deficient Anemia: Narrative Review and Practical Reflections through A Teaching Case

Marialuisa Zedde, Giacomo Portaro, Laura Ferri, Francesco Cavallieri, Manuela Napoli, Claudio Moratti, Fabrizio Piazza, Franco Valzania, Rosario Pascarella

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: iron-deficient anemia; IDA; stroke; cerebral venous thrombosis; brain MRI; aortic thrombosis; pulmonary embolism; embolic pattern

Online: 10 August 2022 (04:31:26 CEST)

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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.

Preprint CASE REPORT | doi:10.20944/preprints202208.0165.v1

A Rare Case of Idiopathic Painful Nervus Intermedius Neuropathy in a 13-Year-Old Female: A Case Report and Discussion in the Context of the Literature

Diego Fernandez-Vial, Linda Sangalli, Cristina Perez

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: neuralgia; earache; facial pain; neuropathic pain; geniculate neuralgia; nervus intermedius; otalgia; gabapentin

Online: 9 August 2022 (03:20:29 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202208.0161.v1

Effects of Crocin on Brain Neurotrophins, Cognition, Sensory and Motor Dysfunction in Rats Demyelination with Ethidium Bromide

Rouholah Fatemi, Hadi Fathimoghadam, Atatalah Ghadiri, Yaghoub Farbod

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Crocin; Multiple scleroses; Cognition; BDNF; NGF; Demyelination

Online: 8 August 2022 (13:46:09 CEST)

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Medicine and Pharmacology