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Cells Jun 2020Key pathological features of cerebral small vessel disease (cSVD) include impairment of the blood brain barrier (BBB) and the progression of white matter lesions (WMLs)...
Key pathological features of cerebral small vessel disease (cSVD) include impairment of the blood brain barrier (BBB) and the progression of white matter lesions (WMLs) amongst other structural lesions, leading to the clinical manifestations of cSVD. The function of endothelial cells (ECs) is of major importance to maintain a proper BBB. ECs interact with several cell types to provide structural and functional support to the brain. Oligodendrocytes (OLs) myelinate axons in the central nervous system and are crucial in sustaining the integrity of white matter. The interplay between ECs and OLs and their precursor cells (OPCs) has received limited attention yet seems of relevance for the study of BBB dysfunction and white matter injury in cSVD. Emerging evidence shows a crosstalk between ECs and OPCs/OLs, mediated by signaling through the Wingless and Int-1 (WNT)/β-catenin pathway. As the latter is involved in EC function (e.g., angiogenesis) and oligodendrogenesis, we reviewed the role of WNT/β-catenin signaling for both cell types and performed a systematic search to identify studies describing a WNT-mediated interplay between ECs and OPCs/OLs. Dysregulation of this interaction may limit remyelination of WMLs and render the BBB leaky, thereby initiating a vicious neuroinflammatory cycle. A better understanding of the role of this signaling pathway in EC-OL crosstalk is essential in understanding cSVD development.
Topics: Cerebral Small Vessel Diseases; Endothelial Cells; Humans; Oligodendroglia; Wnt Signaling Pathway
PubMed: 32630426
DOI: 10.3390/cells9061545 -
Journal of Clinical Medicine Feb 2023Critically sized nerve defects cause devastating life-long disabilities and require interposition for reconstruction. Additional local application of mesenchymal stem...
Critically sized nerve defects cause devastating life-long disabilities and require interposition for reconstruction. Additional local application of mesenchymal stem cells (MSCs) is considered promising to enhance peripheral nerve regeneration. To better understand the role of MSCs in peripheral nerve reconstruction, we performed a systematic review and meta-analysis of the effects of MSCs on critically sized segment nerve defects in preclinical studies. 5146 articles were screened following PRISMA guidelines using PubMed and Web of Science. A total of 27 preclinical studies (n = 722 rats) were included in the meta-analysis. The mean difference or the standardized mean difference with 95% confidence intervals for motor function, conduction velocity, and histomorphological parameters of nerve regeneration, as well as the degree of muscle atrophy, was compared in rats with critically sized defects and autologous nerve reconstruction treated with or without MSCs. The co-transplantation of MSCs increased the sciatic functional index (3.93, 95% CI 2.62 to 5.24, < 0.00001) and nerve conduction velocity recovery (1.49, 95% CI 1.13 to 1.84, = 0.009), decreased the atrophy of targeted muscles (gastrocnemius: 0.63, 95% CI 0.29 to 0.97 = 0.004; triceps surae: 0.08, 95% CI 0.06 to 0.10 = 0.71), and promoted the regeneration of injured axons (axon number: 1.10, 95% CI 0.78 to 1.42, < 0.00001; myelin sheath thickness: 0.15, 95% CI 0.12 to 0.17, = 0.28). Reconstruction of critically sized peripheral nerve defects is often hindered by impaired postoperative regeneration, especially in defects that require an autologous nerve graft. This meta-analysis indicates that additional application of MSC can enhance postoperative peripheral nerve regeneration in rats. Based on the promising results in vivo experiments, further studies are needed to demonstrate potential clinical benefits.
PubMed: 36835844
DOI: 10.3390/jcm12041306 -
Frontiers in Neuroscience 2022Sensory corpuscles, or cutaneous end-organ complexes, are complex structures localized at the periphery of Aβ-axon terminals from primary sensory neurons that primarily...
Sensory corpuscles, or cutaneous end-organ complexes, are complex structures localized at the periphery of Aβ-axon terminals from primary sensory neurons that primarily work as low-threshold mechanoreceptors. Structurally, they consist, in addition to the axons, of non-myelinating Schwann-like cells (terminal glial cells) and endoneurial- and perineurial-related cells. The terminal glial cells are the so-called lamellar cells in Meissner and Pacinian corpuscles. Lamellar cells are variably arranged in sensory corpuscles as a "coin stack" in the Meissner corpuscles or as an "onion bulb" in the Pacinian ones. Nevertheless, the origin and protein profile of the lamellar cells in both morphotypes of sensory corpuscles is quite similar, although it differs in the expression of mechano-gated ion channels as well as in the composition of the extracellular matrix between the cells. The lamellar cells have been regarded as supportive cells playing a passive role in the process of genesis of the action potential, i.e., the mechanotransduction process. However, they express ion channels related to the mechano-electric transduction and show a synapse-like mechanism that suggest neurotransmission at the genesis of the electrical action potential. This review updates the current knowledge about the embryonic origin, development modifications, spatial arrangement, ultrastructural characteristics, and protein profile of the lamellar cells of cutaneous end-organ complexes focusing on Meissner and Pacinian morphotypes.
PubMed: 35356056
DOI: 10.3389/fnins.2022.790130 -
Multiple Sclerosis and Related Disorders Dec 2022Myelin oligodendrocyte glycoprotein (MOG) antibodies mediate inflammatory demyelinating diseases of the central nervous system. This study aimed to understand the...
BACKGROUND
Myelin oligodendrocyte glycoprotein (MOG) antibodies mediate inflammatory demyelinating diseases of the central nervous system. This study aimed to understand the clinical characteristics of MOG antibody-associated aseptic meningitis (MOGAM).
METHODS
Here, we report the cases of two children with MOGAM. A systematic literature review was conducted and included patients who had MOGAM only, without neurological parenchymal lesions. The clinical characteristics that may have affected the outcome were statistically analyzed.
RESULTS
We reviewed 12 cases of MOGAM; male: female = 9: 3. Prolonged fever lasting over 7 days (11/12) was the most frequent symptom, followed by headache (10/12), vomiting (5/12), and seizures (4/12). None of the patients had focal neurological manifestations or parenchymal lesions on imaging. Cerebrospinal fluid (CSF) leukocytosis was observed in all patients (12/12), and blood leukocytosis and elevated CSF pressure was observed in all patients who had corresponding results (9/9 and 4/4, respectively). Seizures occurrence was lower than that of MOG antibody-associated cortical encephalitis. Seven cases progressed to other MOG antibody-associated diseases (MOGADs) in the later phase of MOGAM. Patients who did not progress to other MOGADs had a shorter disease duration from onset to the initiation of intravenous methylprednisolone than those who did. All the patients achieved full recovery after steroid treatment. One patient had relapses.
CONCLUSIONS
MOGAM without inflammatory demyelination is a rare but distinct phenotype of MOGAD, with fewer clinical manifestations mimicking bacterial or viral meningitis/encephalomeningitis. Delayed diagnosis and treatment may induce the progression to other severe MOGADs. Early recognition of this unique autoimmune aseptic meningitis may contribute to early diagnosis, treatment, and better outcomes.
Topics: Female; Humans; Male; Autoantibodies; Encephalitis; Meningitis, Aseptic; Myelin-Oligodendrocyte Glycoprotein; Seizures; Child
PubMed: 36115288
DOI: 10.1016/j.msard.2022.104126 -
Nutrients Mar 2020Gluten-related neurological disorders (GRND) represent a spectrum of neurological manifestations that are triggered by gluten. In coeliac disease, a T-cell mediated... (Meta-Analysis)
Meta-Analysis
Gluten-related neurological disorders (GRND) represent a spectrum of neurological manifestations that are triggered by gluten. In coeliac disease, a T-cell mediated enteropathy is triggered by gluten in genetically predisposed individuals. The underlying pathological mechanism of the neurological dysfunction is not yet clear. The aim of this review is to collate existing neuropathological findings in GRND as a means of aiding the understanding of the pathophysiology. A systematic search of the Pubmed Database yielded 188 articles, of which 32 were included, containing 98 eligible cases with a description of pathological findings in GRND. In gluten ataxia, loss of Purkinje cells, atrophy, gliosis and astrocytosis were apparent, as well as diffuse lymphocytic infiltration and perivascular cuffing with lymphocytes. In patients with large-fiber neuropathy, nerve biopsies revealed axonopathy, loss of myelinated fibers and focal and perivascular infiltration by inflammatory cells. Inflammatory infiltrate was also observed in muscle in myopathy and in cerebrum of patients with encephalopathy and patients with epilepsy. Such changes were not seen in skin biopsies from patients with small fiber neuropathies. The findings from this systematic review suggest an immune mediated pathogenesis for GRND. Future research should focus on the characterization of the inflammatory cell infiltrates and identifying target epitopes.
Topics: Biomarkers; Disease Management; Disease Susceptibility; Glutens; Humans; Immunohistochemistry; Nervous System Diseases; Organ Specificity; Phenotype
PubMed: 32244870
DOI: 10.3390/nu12030822 -
Frontiers in Neuroscience 2020Degenerative cervical myelopathy (DCM), also known as cervical spondylotic myelopathy is the leading cause of spinal cord compression in adults. The mainstay of...
Degenerative cervical myelopathy (DCM), also known as cervical spondylotic myelopathy is the leading cause of spinal cord compression in adults. The mainstay of treatment is surgical decompression, which leads to partial recovery of symptoms, however, long term prognosis of the condition remains poor. Despite advances in treatment methods, the underlying pathobiology is not well-known. A better understanding of the disease is therefore required for the development of treatments to improve outcomes following surgery. To systematically evaluate the pathophysiology of DCM and the mechanism underlying recovery following decompression. A total of 13,808 published articles were identified in our systematic search of electronic databases (PUBMED, WEB OF SCIENCE). A total of 51 studies investigating the secondary injury mechanisms of DCM or physiology of recovery in animal models of disease underwent comprehensive review. Forty-seven studies addressed the pathophysiology of DCM. Majority of the studies demonstrated evidence of neuronal loss following spinal cord compression. A number of studies provided further details of structural changes in neurons such as myelin damage and axon degeneration. The mechanisms of injury to cells included direct apoptosis and increased inflammation. Only four papers investigated the pathobiological changes that occur in spinal cords following decompression. One study demonstrated evidence of axonal plasticity following decompressive surgery. Another study demonstrated ischaemic-reperfusion injury following decompression, however this phenomenon was worse when decompression was delayed. In preclinical studies, the pathophysiology of DCM has been poorly studied and a number of questions remain unanswered. The physiological changes seen in the decompressed spinal cord has not been widely investigated and it is paramount that researchers investigate the decompressed spinal cord further to enable the development of therapeutic tools, to enhance recovery following surgery.
PubMed: 32425740
DOI: 10.3389/fnins.2020.00138 -
Drug and Alcohol Dependence Aug 2019Converging lines of evidence from diffusion tensor imaging (DTI) studies reveal significant alterations in white matter (WM) microstructure in the prefrontal cortex of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Converging lines of evidence from diffusion tensor imaging (DTI) studies reveal significant alterations in white matter (WM) microstructure in the prefrontal cortex of chronic stimulant users compared to controls, suggesting compromised axonal microstructure and/or myelin.
METHODS
A meta-analysis of DTI-based WM integrity was conducted for white matter regions across the corpus callosum and association fibers. Articles were sourced and selected using PRISMA guidelines for systematic review and meta-analysis. Inclusion and exclusion criteria were determined by the authors in order to best capture WM integrity among individuals with primary stimulant use in comparison to healthy control subjects.
RESULTS
Eleven studies that focused on region-of-interest (ROI)-based analysis of WM integrity were extracted from an initial pool of 113 independent studies. Analysis across ROIs indicated significantly lower fractional anisotropy (FA) values in stimulant use groups compared to controls with a small to moderate overall effect (Hedges' g = -0.37, 95% CI [-0.54, -0.20]). Eigenvalues were also analyzed, revealing a significant effect for radial diffusivity (RD; Hedges' g = 0.24, 95% CI [0.01, 0.47]) but not axial diffusivity (AD; Hedges' g = 0.05, 95% CI [-0.20, 0.29]) or mean diffusivity (MD; Hedges' g = 0.20, 95% CI [-0.01, 0.41]). Subgroup analyses based on specific ROIs, primary substance use, poly-substance use, and imaging technology were also explored.
CONCLUSION
Results of the present study suggest a consistent effect of compromised WM integrity for individuals with stimulant use disorders. Furthermore, no significant differences were found between cocaine and methamphetamine-based groups.
Topics: Adult; Amphetamine-Related Disorders; Anisotropy; Central Nervous System Stimulants; Corpus Callosum; Diffusion Tensor Imaging; Female; Humans; Male; Prefrontal Cortex; White Matter
PubMed: 31176066
DOI: 10.1016/j.drugalcdep.2019.03.023 -
Neurology(R) Neuroimmunology &... Jan 2022The objective of the retrospective analysis was to test the hypothesis that changes in serum anti-myelin-associated glycoprotein (MAG) autoantibodies are associated with... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
The objective of the retrospective analysis was to test the hypothesis that changes in serum anti-myelin-associated glycoprotein (MAG) autoantibodies are associated with clinical response to immunotherapy in patients with anti-MAG neuropathy.
METHODS
As of January 29, 2020, we used anti-myelin-associated glycoprotein-related search strings in the Medline database to identify studies that provided information on anti-MAG immunoglobulin M (IgM) autoantibodies and clinical outcomes during immunotherapies. The relative change in anti-MAG IgM titers, paraprotein levels, or total IgM was determined before, during, or posttreatment, and the patients were assigned to "responder," "nonresponder,"' or "acute deteriorating" category depending on their clinical response to treatment. The studies were qualified as "supportive" or "not supportive" depending on the percentage of patients exhibiting an association between relative change of anti-MAG antibody titers or levels and change in clinical outcomes.
RESULTS
Fifty studies with 410 patients with anti-MAG neuropathy were included in the analysis. Forty studies with 303 patients supported the hypothesis that a "responder" patient had a relative reduction of anti-MAG antibody titers or levels that is associated with clinical improvements and "nonresponder" patients exhibited no significant change in anti-MAG IgM antibodies. Six studies with 93 patients partly supported, and 4 studies with 26 patients did not support the hypothesis.
DISCUSSION
The retrospective analysis confirmed the hypothesis that a relative reduction in serum anti-MAG IgM antibodies is associated with a clinical response to immunotherapies; a sustained reduction of at least 50% compared with pretreatment titers or levels could be a valuable indicator for therapeutic response.
Topics: Aged; Autoantibodies; Autoimmune Diseases of the Nervous System; Female; Humans; Immunologic Factors; Male; Middle Aged; Myelin-Associated Glycoprotein; Retrospective Studies
PubMed: 34759022
DOI: 10.1212/NXI.0000000000001109 -
Frontiers in Medicine 2023To improve comprehension of initial brain growth in wellness along with sickness, it is essential to precisely segment child brain magnetic resonance imaging (MRI) into...
INTRODUCTION
To improve comprehension of initial brain growth in wellness along with sickness, it is essential to precisely segment child brain magnetic resonance imaging (MRI) into white matter (WM) and gray matter (GM), along with cerebrospinal fluid (CSF). Nonetheless, in the isointense phase (6-8 months of age), the inborn myelination and development activities, WM along with GM display alike stages of intensity in both T1-weighted and T2-weighted MRI, making tissue segmentation extremely difficult.
METHODS
The comprehensive review of studies related to isointense brain MRI segmentation approaches is highlighted in this publication. The main aim and contribution of this study is to aid researchers by providing a thorough review to make their search for isointense brain MRI segmentation easier. The systematic literature review is performed from four points of reference: (1) review of studies concerning isointense brain MRI segmentation; (2) research contribution and future works and limitations; (3) frequently applied evaluation metrics and datasets; (4) findings of this studies.
RESULTS AND DISCUSSION
The systemic review is performed on studies that were published in the period of 2012 to 2022. A total of 19 primary studies of isointense brain MRI segmentation were selected to report the research question stated in this review.
PubMed: 38193036
DOI: 10.3389/fmed.2023.1240360 -
Neurologia Oct 2018Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system. MS is characterised by nerve demyelination that can alter nerve transmission...
INTRODUCTION
Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system. MS is characterised by nerve demyelination that can alter nerve transmission and lead to such symptoms as fatigue, muscle weakness, and impaired motor function. There are 47 000 people with MS in Spain. Vibration training can be an effective and complementary alternative to traditional exercise to treat patients with MS. The aim of this study was to analyse the effectiveness of vibration training programmes in patients with MS.
DEVELOPMENT
We searched 5 electronic databases (PubMed, SPORTDiscus, SciELO, Lilacs, IBECS, and ISI Web of Knowledge) in August 2015. By using a set of keywords, we found studies linking vibration training and MS and included randomised controlled trials that applied vibration training to patients with MS. Our search yielded 71 studies. Only 9 of them were included after removing duplicate studies and those which were not relevant according to our selection criteria. These studies obtained different outcomes.
CONCLUSIONS
Some studies found improvements in muscle strength, functional capacity, coordination, resistance, balance, and some areas of MSSS-88. However, we identified limitations in some of these studies and there are still few publications on vibration training and multiple sclerosis to ensure training effectiveness.
Topics: Humans; Multiple Sclerosis; Physical Therapy Modalities; Randomized Controlled Trials as Topic; Vibration
PubMed: 27448520
DOI: 10.1016/j.nrl.2016.04.007