REVIEW | doi:10.20944/preprints202111.0064.v1
Subject: Medicine & Pharmacology, Other Keywords: primary headache; migraine; trigeminal system; neuropeptides; neurogenic inflammation; animal model; inflammatory soup; dura mater; immune system; migraine treatment
Online: 3 November 2021 (08:30:58 CET)
Migraine is a primary headache disorder characterized by unilateral throbbing, pulsing headache, which lasts for hours to days, and the pain can interfere with daily activities. It exhibits various symptoms, such as nausea, vomiting, sensitivity to light, sound, and odors and physical activity consistently contributes to worsening pain. Despite the intensive research, little is still known about the pathomechanism of migraine. It is widely accepted that migraine involves activation and sensitization of the trigeminovascular system. It leads to the release of several pro-inflammatory neuropeptides and neurotransmitters and causes a cascade of inflammatory tissue responses including vasodilation, plasma extravasation secondary to capillary leakage, edema, and mast cell degranulation. Convincing evidence obtained in rodent models suggests that neurogenic inflammation is assumed to contribute to the development of a migraine attack. Chemical stimulation of the dura mater triggers activation and sensitization of the trigeminal system and causes numerous molecular and behavioral changes; therefore, this is a relevant animal model of acute migraine. This review article discusses the emerging evidence supporting the involvement of neurogenic inflammation and neuropeptides in the pathophysiology of migraine, presenting the most recent advances in preclinical research and the novel therapeutic approaches to the disease.
REVIEW | doi:10.20944/preprints202210.0083.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: epigenetics; TRP channels; TRPA1; pain transmission; neuropathic pain; neurogenic inflammation; migraine; DNA methylation; histone modification; micro RNA
Online: 7 October 2022 (15:21:34 CEST)
Background: Transient receptor potential cation channel subfamily A member 1 (TRPA1) is expressed in trigeminal neurons and brain regions important in migraine pathogenesis and is activated by many migraine triggers. Epigenetic regulation of TRPA1 expression is important in pain transmission and neurogenic inflammation.Findings: TRPA1 channels change noxious stimuli into pain signals with the involvement of epigenetic regulation, including DNA methylation, histone modifications, and effects of micro RNAs (miRNAs) and long non-coding RNAs. TRPA1 may change epigenetic profile of many pain-related genes as it may modify enzymes establishing the epigenetic profile and expression of non-coding RNAs. TRPA1 may induce the release of calcitonin gene related peptide (CGRP), from trigeminal neurons and dural tissue. Therefore, epigenetic regulation of TRPA1 may play a role in efficacy and safety of anti-migraine therapies targeting TRP channels and CGRP. TRPA1 is also involved in neurogenic inflammation, important in migraine. The fundamental role of TRPA1 in inflammatory pain transmission may be epigenetically regulated. Conclusions: Epigenetic connections of TRPA1 may play a role in efficacy and safety of anti-migraine therapy targeting TRP channels or CGRP and they should be further explored for efficient and safe antimigraine treatment.
ARTICLE | doi:10.20944/preprints202208.0122.v1
Subject: Medicine & Pharmacology, Other Keywords: neurogenic potential; neurites; SCAPs; sphere; stem cells
Online: 5 August 2022 (09:59:07 CEST)
Abstract: Cell-based neural regeneration is challenging due to the difficulty in obtaining sufficient neural stem cells with clinical applicability. SCAPs originating from embryonic neural crest with high neurogenic potential could be a promising cell source for neural regeneration. This study aimed to investigate whether the formation of 3D spheres can promote SCAPs neurogenic potential. Material and methods: 3D SCAPs spheres were first generated in 256-well agarose microtissue mold. The spheres and single cells were individually cultured on collagen I coated μ-Slide for 4 and 7 days. Cell morphological changes, neural marker expression, and neurite outgrowth were evaluated under a confocal microscope. Secretion of BDNF and NGF-β was measured by ELISA kits. Results: Pronounced morphological changes were noticed in a time-dependent manner. The migrating cells’ morphology changed from fibroblast-like cells to neuron-like cells. Compared to the 2D culture, neurite length, number, and the expression of neural markers, including Nestin, β-tubulin III, NeuN, and MAP-2 were significantly increased in the 3D spheres, while the secretion of BDNF and NGF-β was markedly downregulated at day 7. Conclusion: The formation of 3D spheres enhanced the neurogenic potential of SCAPs, suggesting the advantage of using the 3D spheres of SCAPs for the treatment of neural diseases.
ARTICLE | doi:10.20944/preprints201807.0424.v1
Subject: Medicine & Pharmacology, Urology Keywords: neurogenic bladder, botulinum toxin, bladder overactivity, urodynamics, child
Online: 23 July 2018 (12:48:56 CEST)
The aim of this study was to evaluate the usefulness of cystoscopic injection of Botulinum-A toxin (BTX) in the detrusor wall in the treatment of children with decreased bladder capacity due to neurogenic bladder. The prospective, randomized non placebo controlled trial is conducted in our institution since year 2006 with the approval of the local Ethics Committee. 556 cystoscopic injections of BTX were performed in 141 children with neurogenic bladder in age 1 to 18 years. In all cases decreased bladder capacity and bladder overactivity with urine incontinence were estimated. The pre-and post-treatment evaluations included determination of urinary continence status, bladder function in frequency/volume chart of catheterized urine and in urodynamic studies. Parameters measured in urodynamic investigations included maximal cystometric capacity, detrusor reflex volume, maximal detrusor pressure. Parameters were analyzed before the cystoscopy and during the follow-up examinations in 5 age groups. Values of all measured parameters improved significantly and equally after therapy in every from 5 age groups. The results obtained from the study confirmed that endoscopic administration of BTX improves function of urinary bladder in children with neurogenic bladder, and the method represents an alternative approach to conservative treatment and surgical augmentation.
ARTICLE | doi:10.20944/preprints201611.0133.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: GH; syndrome of caudal regression; sacral agenesis; physiotherapy; neurogenic bladder; flaccid paraplegia
Online: 27 November 2016 (04:35:36 CET)
Caudal regression syndrome (CRS) is a congenital abnormality characterized by an incomplete development of the spinal cord (SC) and other abnormalities. We studied a 9-months old CRS child presenting: interruption of SC at L2-L3 level, sacral agenesis, lack of innervation of the inferior limbs (flaccid paraplegia) and neurogenic bladder and bowel. Given the effects of growth hormone (GH) on the proliferation, differentiation and migration of neural stem cells (NSCs), we treated him with GH and rehabilitation, trying to induce the recovery of main sequelae. GMFM-88 test score was 12.31%. After a blood analysis, GH treatment (0.3 mg/day, 5 days/week, 3 months and then 15 days without GH) and rehabilitation commenced. This protocol was followed during 5 years, being the last GH dose 1 mg/day. Blood analysis and physical exams were performed every 3 months initially and every 6 months later. Six months after commencing the treatment GMFM-88 score increased to 39.48%. Responses to sensitive stimuli appeared in most of the territories explored; 18 months later sensitive innervation was complete and the patient moved any muscle over the knees and controlled his sphincters. Three years later he walked with the help of canes, there was plantar flexion and GMFM-88 score was 78.48%. In summary, GH plus rehabilitation may be useful for innervating distal territories, below the level of the incomplete spinal cord in CRS. Most likely, GH acts on ependymal SC NSCs, as the hormone does in the neurogenic niches in the brain.