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Astrocyte CB1 receptors drive blood-brain barrier disruption in central nervous system inflammatory disease.

Reactive astrocytes shape central nervous system (CNS) inflammation and participate in myelin damage and repair mechanisms in multiple sclerosis (MS). Through the activation of cannabinoid CB1 receptors (CB1R) expressed by neurons and oligodendrocyte lineage cells, endocannabinoid signaling restricts neurodegeneration and promotes remyelination in preclinical MS models. However, despite accumulating evidence that supports cell-specific roles for CB1R in brain physiology and pathology, the implications of astrocyte CB1R signaling in MS initiation and progression remain uncertain. Using compleme…

Alcohol induces concentration-dependent transcriptomic changes in oligodendrocytes.

Oligodendrocytes are a key cell type within the central nervous system (CNS) that generates the myelin sheath covering axons, enabling fast … rthermore, gaining a deeper understanding of alcohol's effects on oligodendrocyte demyelination and remyelination could help uncover therapeutic pathways that can be utilized independently of alcohol to aid in remyelinating drug design.

Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons.

Oligodendrocytes and astrocytes are metabolically coupled to neuronal compartments. Pyruvate and lactate can shuttle between glial cells and … oligodendrocytes. Our data suggest that oligodendrocytes metabolize lactate during development and remyelination. In contrast, for metabolic support of axons mature oligodendrocytes may export their own glycolysis products as pyruvate rather than lactate. Lacking LDH, these oligodendrocytes can also "funnel" lactate through their "myelinic" channels between ga …

Iron promotes neurological function recovery in mice with ischemic stroke through endogenous repair mechanisms.

The endogenous repair mechanisms play an important role in the recovery of nerve function after stroke, such as gliosis, synaptic plasticity, remyelination and nerve regeneration. Iron is the most abundant trace metal element in the brain and plays a crucial role in the maintenance of normal cerebral function. It is an important coenzyme factor in the process of cell metabolism, DNA synthesis, purine catabolism and neurotransmitter synthesis and decomposition. However, it is unclear what role iron plays in the long-term recovery of neurological function after stroke. In this study, we first ob…

Improvement of peripheral nerve regeneration following immunological demyelination in vivo.

BACKGROUND: To improve regeneration of the peripheral nervous system, a therapy was utilized in the adult rat sciatic nerve in which nerve r … t proteins plus antibodies to galactocerebroside resulted in demyelination followed by Schwann cell remyelination. At 14 days, remyelination was demonstrated spanning the injured sciatic nerve segment. At 28 days, peripheral nerve regeneration was quantified by total axon count, axon density, and nerve fiber diameter. Tracers demonstrated that regeneration aros …

Cervical spondylotic myelopathy. Clinicopathologic study on the progression pattern and thin myelinated fibers of the lesions of seven patients examined during complete autopsy.

STUDY DESIGN: This study was designed to reveal the progression pattern and essential histological findings of the lesions in the spinal cord affected by cervical spondylotic myelopathy. OBJECTIVES: The purpose of this study was to gain new information about symptom progression and recovery in cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: The characteristics of the distribution and the progression pattern of the lesions and whether demyelination and remyelination processes actually occur in cervical spondylotic myelopathy remain unclear. METHODS: Tissues from seven patients w…

Aging, regeneration, and peripheral nerve repair: Integrated multi-omics biomarkers and AI-enabled therapeutic discovery approaches.

Peripheral nerve injury (PNI) remains a major cause of long-term sensory and motor dysfunction, imposing a substantial clinical and socioeconomic burden worldwide. Although peripheral nerves possess intrinsic regenerative capacity, functional recovery is often incomplete because of the complex interplay among axonal degeneration, Schwann cell plasticity, neuroimmune responses, extracellular matrix remodeling, metabolic reprogramming, remyelination, and target reinnervation. Recent advances in transcriptomics, proteomics, epigenomics, metabolomics, and single-cell technologies have expanded mol…

Острая интермитуционная гипоксия выделяет положительные эффекты и содействует ремонту в мужских мышах в экспериментальной модели аутоиммунного энцефаломиелита множественного склероза.

Множественный склероз (МС) затрагивает женщин чаще, чем мужчин, однако у мужчин болезнь развивается более агрессивно. Мы продемонстрировали, что острая периодическая гипоксия (AIG), неинвазивная терапия, способствует ремонту и ремииляции и изменяет курс по болезням в женской модели MOG35-55 (экспериментальная аутоиммунная энцефаломиелит (EAE) MS. С учетом важности понимания принимаемых с учетом пола мер реагирования на потенциальные методы лечения MS, мы изучили вопрос о том, оказывает ли AIG аналогичное терапевтическое воздействие на самцов мышей EAE. EAE была вызвана иммунизацией MOG35-55 в

Совпадение в аннотации оригинала
Multiple sclerosis (MS) affects women more frequently than men, but the disease progresses more aggressively in men. We have demonstrated that acute intermittent hypoxia (AIH), a noninvasive therapy, promotes repair and remyelination and alters disease course in the female MOG35-55 experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Given the …

Single-nuclei RNA sequencing unveils astrocyte and oligodendrocyte lineage cells in post-stroke human brain.

BACKGROUND: Ischemic stroke (IS) induces profound, region-specific shifts in cellular composition and gene expression, particularly within g … e analysis indicated a shift of OPCs toward earlier lineage states and trajectories consistent with remyelination after IS. Synaptic pathway enrichment with unchanged PSD95 and SYN levels suggests transcriptional glial-neuronal regulation rather than large-scale synaptic protein alteration. Validation by WB, qPCR, and IF confirmed the translational relevance of …

Эпигенетика и метаболическая метаболическая дисфункция при многоразовом склерозе: обзор подходов к травяным лекарствам и текущих клинических испытаний.

Множественный склероз (MS) — сложная аутоиммунная болезнь, характеризующаяся воспалением, обезвоживанием и нейродегенерацией в центральной нервной системе (КНС). Хотя точные причины остаются неясными, недавние исследования подчеркивают важную роль эпигенетических изменений и митохондриальной дисфункции в начале и развитии болезни. Эпигенетические изменения, такие, как метилация ДНК, модификация гистона и регулирование микроРНК, влияют на генное выражение, не изменяя последовательности ДНК, что приводит к иммунной дисрегуляции и воспалению. Аналогичным образом, митохондриальная дисфункция, отме

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a complex autoimmune disease characterised by inflammation, demyelination, and neurodegeneration within the centr … duction, and increased reactive oxygen species (ROS), contributes to neurodegeneration and impaired remyelination in MS. The growing interest in targeting these two interconnected mechanisms has opened new avenues for MS treatment. Herbal drugs, known for their multi-targeted effects, have shown potential in modulating epigenetic markers and enhancing mitochond …

Therapeutic Effect of Schwann Cell-Like Cells Differentiated from Human Tonsil-Derived Mesenchymal Stem Cells on Diabetic Neuropathy in db/db Mice.

BACKGROUND: Diabetic neuropathy (DN) is the most common complication of diabetes, and approximately 50% of patients with this disease suffer … ment group (NRPC group) showed faster responses to less force than the vehicle group. Additionally, remyelination of sural nerve fibers also increased in the NRPC group. After NRPCs treatment, an improvement in response to external stimuli and pain sensation was expected through increased expression of PGP9.5 in the sole and TRPV1 in the DRG. CONCLUSION: The N …

Nalfurafine promotes myelination in vitro and facilitates recovery from cuprizone + rapamycin-induced demyelination in mice.

The kappa opioid receptor has been identified as a promising therapeutic target for promoting remyelination. In the current study, we evaluated the ability of nalfurafine to promote oligodendrocyte progenitor cell (OPC) differentiation and myelination in vitro, and its efficacy in an extended, cuprizone-induced demyelination model. Primary mouse (C57BL/6J) OPC-containing cultures were treated with nalfurafine (0.6-200 nM), clemastine (0.01-100 μM), T3 (30 ng/mL), or vehicle for 5 days. Using immunocytochemistry and confocal microscopy, we found that nalfurafine treatment increased OPC differen…

Pathophysiological basis of low contrast visual acuity loss in multiple sclerosis.

OBJECTIVE: There is currently an urgent need for reliable clinical biomarkers of remyelination to be used in Phase 2 and Phase 3 clinical trials. Low contrast visual acuity (LCVA) has been suggested as a functional measure of the integrity of the visual pathway. Therefore, the aim of this study was to elucidate the potential contribution of axonal loss and demyelination to LCVA loss in MS patients. METHOD: In this study, 50 consecutive relapsing remitting MS patients with a previous history of unilateral optic neuritis were enrolled. Using the linear regression model, we assessed the relative…

Parallel changes in structural and functional measures of optic nerve myelination after optic neuritis.

INTRODUCTION: Visual evoked potential (VEP) latency prolongation and optic nerve lesion length after acute optic neuritis (ON) corresponds to the degree of demyelination, while subsequent recovery of latency may represent optic nerve remyelination. We aimed to investigate the relationship between multifocal VEP (mfVEP) latency and optic nerve lesion length after acute ON. METHODS: Thirty acute ON patients were studied at 1, 3, 6 and 12 months using mfVEP and at 1 and 12 months with optic nerve MRI. LogMAR and low contrast visual acuity were documented. By one month, the mfVEP amplitude had re…

Function-triggering antibodies to the adhesion molecule L1 enhance recovery after injury of the adult mouse femoral nerve.

L1 is among the few adhesion molecules that favors repair after trauma in the adult central nervous system of vertebrates by promoting neuri … rotrophic factors. On the other hand, transgenic mice over-expressing L1 in neurons led to improved remyelination, but not improved functional recovery. The present study was undertaken to investigate whether the monoclonal L1 antibody 557 that triggers beneficial L1 functions in vitro would trigger these also in femoral nerve repair. We analyzed femoral nerve …

Medical rehabilitation of chronic progressive disseminated encephalomyelitis (MS).

Eight years after diagnosis, 40% of MS patients develop a chronically progressive form. Annually we treat approximately 200 patients with pr … sunflower oil), sufficient protein, and freshly prepared fruits and vegetables as a sound basis for remyelination. Remyelination profits from general prophylaxis in the use of ascorbic acid to help prevent urinary infections via acidification, autogenic training to reduce fatigue, improve ventilation of deeper airways, and stimulate vagotonic regeneration, and …

Spastic syndrome in a Holstein bull: a histologic study.

A 4-year-old Canadian holstein bull developed the spastic syndrome, an episodic but progressive disorder causing pelvic limb muscular spasms. A post-mortem study, including morphometry of skeletal muscles and teased peripheral nerve fibers of the pelvic limb, revealed mild type II skeletal muscle fiber atrophy and minimal, focal segmental demyelination with remyelination, and axonal degeneration in peripheral nerves. Such alterations are probably incidental or age-associated. Idiopathic muscular cramps is the most probable explanation of the clinical disease and is consistent with the absence …

Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial.

BACKGROUND: The human monoclonal antibody opicinumab (BIIB033, anti-LINGO-1) has shown remyelinating activity in preclinical studies. We the … for preparing the study treatments and the pharmacy monitor at each site. The primary endpoint was remyelination at 24 weeks, measured as recovery of affected optic nerve conduction latency using full-field visual evoked potential (FF-VEP) versus the unaffected fellow eye at baseline. Analysis was by intention-to-treat (ITT); prespecified per-protocol (PP) ana …

From scavenger to victim: mechanism and treatment of microglial ferroptosis in white matter injury disease.

Failure of myelin repair is a shared pathological feature of white matter injury (WMI)-associated diseases, including Alzheimer's disease (AD), vascular dementia (VaD), and multiple sclerosis (MS), but the underlying mechanisms remain incompletely understood. Microglia, the resident innate immune cells of the central nervous system (CNS), contribute to white matter homeostasis by clearing myelin debris and supporting remyelination. Within the iron- and lipid-rich white matter microenvironment, sustained uptake of myelin and oligodendroglial debris may impose phagocytic and metabolic stress on …

Quantitative determination of longitudinal CNS cholesterol loss during myelin damage and repair.

Cholesterol in the central nervous system (CNS) is largely unesterified (>99%) and is predominantly present in the myelin sheath (~70% of total CNS cholesterol). Damage to the myelin sheath can result in the conversion of cholesterol to cholesterol esters, which occurs in many neurological diseases, including multiple sclerosis. In this study, we measured longitudinal CNS free cholesterol and cholesterol ester levels in a genetic mouse model during postnatal myelination, demyelination, and remyelination using gas chromatography-mass spectrometry with single ion monitoring technique (GC-MS-SIM)…