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Chronic demyelination and myelin repair after spinal cord injury in mice: A potential link for glutamatergic axon activity.

Our prior work examining endogenous repair after spinal cord injury (SCI) in mice revealed that large numbers of new oligodendrocytes (OLs) … d a potential mechanism driving OL progenitor cell (OPC) contact with axons. Results reveal peak in remyelination occurs during the 3rd mpi, and that myelin generation continues for at least 6 mpi. Further, motor evoked potentials significantly increased during peak remyelination, suggesting enhanced axon potential conduction. Interestingly, two indices of demy …

Myelin repair of spinal cord injury in adult mice induced by treadmill training upregulated peroxisome proliferator-activated receptor gamma coactivator 1 alpha.

Growing evidence has proven the efficacy of physical exercise in remyelination and motor function performance after spinal cord injury (SCI). However, the molecular mechanisms of treadmill training on myelin repair and functional recovery after SCI have not yet been fully studied. Here, we explored the effect of treadmill training on upregulating peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α)-mediated myelin repair and functional recovery in a mouse model of thoracic T10 contusion injury. A 4-week treadmill training scheme was conducted on mice with SCI. The expre…

Transcriptome Analysis of Schwann Cells at Various Stages of Myelination Implicates Chromatin Regulator Sin3A in Control of Myelination Identity.

Enhancing remyelination after injury is of utmost importance for optimizing the recovery of nerve function. While the formation of myelin by Schwann cells (SCs) is critical for the function of the peripheral nervous system, the temporal dynamics and regulatory mechanisms that control the progress of the SC lineage through myelination require further elucidation. Here, using in vitro co-culture models, gene expression profiling of laser capture-microdissected SCs at various stages of myelination, and multilevel bioinformatic analysis, we demonstrated that SCs exhibit three distinct transcriptio…

Kinetics of myelin breakdown products: A labeling study in patients with progressive multiple sclerosis.

The majority of disease modifying therapies for multiple sclerosis (MS) reduce inflammation, but do no't target remyelination. Development of remyelinating therapies will benefit from a method to quantify myelin kinetics in patients with MS. We labeled myelin in vivo with deuterium, and modeled kinetics of myelin breakdown products β-galactosylceramide (β-GalC) and N-Octadecanoyl-sulfatide (NO-Sulf). Five patients with MS received 120 ml 70% D2 O daily for 70 days and were compared with six healthy subjects who previously received the same procedure. Mass spectrometry and compartmental modelin…

Multiple sclerosis: structural and functional integrity of the visual system following alemtuzumab therapy.

OBJECTIVE: To investigate potential neuroprotective and pro-remyelinating effects of alemtuzumab in multiple sclerosis (MS), using the visua … by an early improvement, in both patients and HC. CONCLUSION: We found evidence of partial lesion remyelination after alemtuzumab therapy, indicating either natural restoration in the context of a 'permissive' local milieu; or potentially an independent, pro-reparative mechanism of action. The visual system presents a unique opportunity to study function-stru …

Membrane metallo-endopeptidase is dispensable for repair after nerve injury.

Membrane metallo-endopeptidase (MME), also known as neprilysin (NEP), has been of interest for its role in neurodegeneration and pain due to … a Neuregulin-1 dependent fashion. We therefore explored the hypothesis that MME may have a role in remyelination. In the naïve state in adulthood we did not find any impairment in myelination in MME KO mice. After nerve injury the morphological outcome in MME KO mice was indistinguishable from WT littermates in terms of axon regeneration and remyelination. We …

Induced Neural Activity Promotes an Oligodendroglia Regenerative Response in the Injured Spinal Cord and Improves Motor Function after Spinal Cord Injury.

Myelination in the central nervous system (CNS) is a dynamic process that includes birth of oligodendrocyte progenitor cells (OPCs), their differentiation into oligodendrocytes, and ensheathment of axons. Regulation of myelination by neuronal activity has emerged as a new mechanism of CNS plasticity. Activity-dependent myelination has been shown to regulate sensory, motor, and cognitive functions. In this work, we aimed to employ this mechanism of CNS plasticity by utilizing induced neuronal activity to promote remyelination and functional recovery in a subchronic model of spinal cord injury (…

Apoptosis of Oligodendrocytes during Early Development Delays Myelination and Impairs Subsequent Responses to Demyelination.

UNLABELLED: During mammalian development, myelin-forming oligodendrocytes are generated and axons ensheathed according to a tightly regulate … ocytes during early postnatal spinal cord development impacted oligodendrogenesis, myelination, and remyelination, transgenic mouse lines were generated in which a modified caspase-9 molecule allowed spatial and temporal control of the apoptotic pathway specifically in mature, myelin basic protein expressing oligodendrocytes (MBP-iCP9). Activating apoptosis in …

Физические упражнения низкой интенсивности связаны с улучшением мелиорации и сокращением микрогранной активации в модели обезвоживания Cuprizone.

Уничтожение таких болезней, как множественный склероз, приводит к повреждению милиновой оболочки, что приводит к неврологическим проблемам. Хотя точные причины НР неясны, известно, что подстрекательские процессы и плохое воспоминание способствуют прогрессированию заболеваний. Упражнения показали, что они являются ненаркотической терапией для MS, и, согласно сообщениям, выгоды для мобильности, настроения и потенциальной нейрозащиты. Однако не в полной мере понимаются конкретные способы воздействия физических упражнений на воспоминание и нейронное воспаление в условиях демиелина. В рамках этого

Совпадение в аннотации оригинала
Demyelinating diseases like multiple sclerosis cause damage to the myelin sheath, leading to neurological problems. While the exact causes of MS are unclear, it is known that inflammatory processes and poor remyelination contribute to disease progression. Exercise has shown promise as a non-drug treatment for MS, with benefits reported for mobility, mood, an…

Pathological potential of oligodendrocyte precursor cells: terra incognita.

Adult oligodendrocyte precursor cells (aOPCs), transformed from fetal OPCs, are idiosyncratic neuroglia of the central nervous system (CNS) that are distinct in many ways from other glial cells. OPCs have been classically studied in the context of their remyelinating capacity. Recent studies, however, revealed that aOPCs not only contribute to post-lesional remyelination but also play diverse crucial roles in multiple neurological diseases. In this review we briefly present the physiology of aOPCs and summarize current knowledge of the beneficial and detrimental roles of aOPCs in different CNS…

Multimodal Evoked Potentials as Candidate Prognostic and Response Biomarkers in Clinical Trials of Multiple Sclerosis.

Evoked potentials (EPs) measure quantitatively and objectively the alterations of central signal propagation in multiple sclerosis and have … vidence for using multimodal EP as prognostic and response biomarkers in clinical trials, targeting remyelination or halting disease progression in multiple sclerosis.

Mechanisms of axon-glial injury of the optic nerve.

The central concept underlying ideas on the pathogenesis of multiple sclerosis is that inflammatory events cause acute injury of axons and myclin. The phases of symptom onset, recovery, persistence, and progression in multiple sclerosis can be summarized as functional impairment with intact structure due to direct effects of inflammatory mediators; demyelination and axonal injury with recovery through plasticity and remyelination; and chronic axonal loss due to failure of enduring remyelination from loss of trophic support for axons normally provided by cells of the oligodendrocyte lineage. Ce…

Use of SEPs to localize degeneration in a rare polyneuropathy: studies on polyneuropathy associated with pigmentation, hypertrichosis, edema, and plasma cell dyscrasia.

Peripheral and cental nerve conduction were studied in five patients who had polyneuropathy associated with pigmentation, hypertrichosis, ed … with the pathological findings, which showed degeneration of axons and segmental demyelination and remyelination in the sural nerve and extensive segmental demyelination and remyelination in the dorsal root but normal posterior columns of the spinal cord. SEP is a noninvasive method of localizing the site of axon or myelin disorder in a peripheral neuropathy.

Failed, Inconclusive or Interrupted Trials in Multiple Sclerosis: 2020-2024 Update.

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation, demyelination, and neuronal loss, with significant public health impact. Despite important therapeutic advances, major unmet needs remain, mainly in targeting neurodegeneration, blocking progression independent of relapse activity and fostering remyelination. Several compounds tested to address some of these processes yielded negative or inconclusive results, forcing researchers, clinicians and industry to look for alternative molecules to alter key underlying pathways. The aim of this study was to examine …

Advancing the Frontiers of Multiple Sclerosis Management: Emerging Immunotherapeutic Strategies.

INTRODUCTION: Multiple Sclerosis (MS) is a chronic neurodegenerative disease characterized by inflammation, demyelination, and neuronal loss … trategies, analyzing preclinical and clinical evidence regarding biologics, neuroprotective agents, remyelination methods, advanced imaging, and biomarker development. RESULTS: Treatment regimens using anti-CD20 monoclonal antibodies such as rituximab, ocrelizumab, and ofatumumab have proven effective in reducing disease activity and slowing progression, espec …

PPAR-γ Is Critical for HDAC3-Mediated Control of Oligodendrocyte Progenitor Cell Proliferation and Differentiation after Focal Demyelination.

Disruption of remyelination contributes to neurodegeneration and cognitive impairment in chronically disabled patients. Valproic acid (VPA) inhibits histone deacetylase (HDAC) function and probably promotes oligodendrocyte progenitor cell (OPC) proliferation and differentiation; however, the relevant molecular mechanisms remain unknown. Here, focal demyelinating lesions (FDLs) were generated in mice by two-point stereotactic injection of lysophosphatidylcholine (LPC) into the corpus callosum. Cognitive functions, sensorimotor abilities and histopathological changes were assessed for up to 28 d…

Optic nerve regeneration in polyglycolic acid-chitosan conduits coated with recombinant L1-Fc.

Autografts have been extensively studied to facilitate optic nerve (ON) regeneration in animal experiments, but the clinical application of … ic acid-chitosan conduit coated with L1-Fc showed more effective to promote axonal regeneration and remyelination. Taken together, our observations demonstrated that the L1-Fc coated PGA-chitosan conduits provided a compatible and supportive canal to guild the injured nerve regeneration and remyelination.

Acetylglutamine facilitates motor recovery and alleviates neuropathic pain after brachial plexus root avulsion in rats.

BACKGROUND: Brachial plexus root avulsion (BPRA), a disabling peripheral nerve injury, induces substantial motoneuron death, motor axon dege … histological staining. Quantitative real-time PCR (qRT‒PCR) was used to measure the mRNA levels of remyelination and regeneration indicators in myocutaneous nerves. The protein levels of inflammatory and pyroptotic indicators in the spinal cord anterior horn were measured using Western blotting. RESULTS: NAG significantly accelerated the recovery of motor fun …

Mesenchymal stem cells enhance the engraftment and myelinating ability of allogeneic oligodendrocyte progenitors in dysmyelinated mice.

Multiple sclerosis is an autoimmune disease characterized by demyelination and axonal loss throughout the central nervous system. No regenerative treatment exists for patients who fail to respond to conventional immunosuppressive and immunomodulating drugs. In this scenario, stem cell therapy poses as a rational approach for neurological regeneration. Transplantation of embryonic-derived oligodendrocyte progenitor cells (OPCs) has been shown to promote remyelination and ameliorate animal models of neurodegenerative diseases. However, its therapeutic application is limited due to potential tran…

Thymosin beta4 promotes oligodendrogenesis in the demyelinating central nervous system.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). No effective remyelination therapies are in use. We hypothesized that thymosin beta4 (Tβ4) is an effective remyelination treatment by promoting differentiation of oligodendrocyte progenitor cells (OPCs), and that the epidermal growth factor receptor (EGFR) signaling pathway contributes to this process. Two demyelination animal models were employed in this study: 1) experimental autoimmune encephalomyelitis (EAE), an animal model of MS. EAE mice were treated daily for 30days, with Tβ4 or saline treatment ini…