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Uncoupled relationship between demyelination and primary infection of myelinating cells in Theiler's virus encephalomyelitis.

Theiler's virus infection in mice produces a chronic demyelinating disease which appears to be based on an immune pathogenesis rather than o … ich follows inoculation with the attenuated ww strain and is characterized by extensive spinal cord remyelination by invading Schwann cells and by recurrent demyelination of Schwann cell-remyelinated axons. The unlabeled antibody peroxidase-antiperoxidase technique was employed to study whether such spinal cord Schwann cells were primarily infected by virus at …

Edaravone Improves Motor Dysfunction Following Brachial Plexus Avulsion Injury in Rats.

Brachial plexus root avulsion (BPRA) is often caused by road collisions, leading to total loss of motor function in the upper limb. At prese … DMD and Caspase-1, improved the morphology of the abnormal myocutaneous nerve fibers, promoted axon remyelination, indicated by increased mRNA expression levels of remyelination-associated genes, including egr2, GAP-43, hmgcr, L1CAM, mpz, pmp22 and prx and demyelination-associated genes, including ngfr, notch1, pou3f1 and sox2, and alleviated muscle atrophy, in …

Fingolimod after a first unilateral episode of acute optic neuritis (MOVING) - preliminary results from a randomized, rater-blind, active-controlled, phase 2 trial.

BACKGROUND: Neuroprotection and promotion of remyelination represent important therapeutic gaps in multiple sclerosis (MS). Acute optic neuritis (ON) is a frequent MS manifestation. Based on the presence and properties of sphingosine-1-phosphate receptors (S1PR) on astrocytes and oligodendrocytes, we hypothesized that remyelination can be enhanced by treatment with fingolimod, a S1PR modulator currently licensed for relapsing-remitting MS. METHODS: MOVING was an investigator-driven, rater-blind, randomized clinical trial. Patients with acute unilateral ON, occurring as a clinically isolated s…

Oligodendrocyte dysfunction in alzheimer's disease: Integrating spatial epigenomics and metabolic circuitry in demyelination - A critical review.

Traditional Alzheimer's disease (AD) research has predominantly focused on neuronal pathology within the amyloid-tau-neurodegeneration (ATN) … trategies that target OL dysfunction, including metabolic rescue approaches, epigenetic modulation, remyelination-oriented interventions, and approaches that suppress OL-derived Aβ. Overall, we propose an "OL epigenetic-metabolic axis" as an underappreciated pathological hub in AD. This framework challengesthe conventional victim-perpetrator narrative by reposi …

In vivo mapping of cortical amyloid beta-myelin coupling in preclinical Alzheimer's disease.

INTRODUCTION: Accumulating evidence suggests that amyloid-β (Aβ) preferentially deposits in poorly myelinated cortical regions and may interfere with remyelination. We hypothesized that this vulnerability would manifest as altered Aβ-myelin coupling in preclinical Alzheimer's disease (AD). METHODS: We assessed spatial coupling between amyloid positron emission tomography (PET) and myelin content estimated from T1w/T2w ratio maps in 151 cognitively unimpaired older adults. Associations with preclinical AD, blood-based biomarkers, resting-state functional connectivity (rs-FC), and subjective me…

Small compounds mimicking the adhesion molecule L1 improve recovery in a zebrafish demyelination model.

Demyelination leads to a loss of neurons, which results in, among other consequences, a severe reduction in locomotor function, and underlies several diseases in humans including multiple sclerosis and polyneuropathies. Considerable clinical progress has been made in counteracting demyelination. However, there remains a need for novel methods that reduce demyelination while concomitantly achieving remyelination, thus complementing the currently available tools to ameliorate demyelinating diseases. In this study, we used an established zebrafish demyelination model to test selected compounds, f…

The neuromuscular pathology of experimental Chagas' disease.

In this work, we describe skeletal muscle, neuromuscular junction, nerve and spinal cord lesions in the mouse model system of Chagas' diseas … . Inflammatory neuropathy was seen in all of the infected mice. Demyelination, axonal degeneration, remyelination and axonal regeneration were observed in the transverse sections. There was an average reduction of 29% in the total number of myelin fibers. The teasing of single myelin fibers showed segmental and paranodal demyelination and remyelination more fre …

Бетен смягчает недостатки в моторном поведении, нейротоксическом воздействии и нейро-воспалительной реакции в крысиной модели обезвоживания.

Множественный склероз (MS) характеризуется как хроническое воспалительное нейродегенеративное расстройство, ведущее к порче милиновой оболочки и потере аксонов. Бетане, триметилглициновое соединение, признается за его способность проникать через барьер мозга крови (ББД) и демонстрирует свойства, которые являются антиоксидантами, антивоспалительными и нейрозащитными. Модель " чапризона " (КПЗ) служит эффективным инструментом для изучения процессов обезвоживания и воспоминания, связанных с НР. В наших исследованиях мы изучили защитные и терапевтические последствия бетаина в крысиной мо

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is characterized as a chronic inflammatory demyelinating neurodegenerative disorder that leads to the deterioration … rizone (CPZ) model serves as an effective tool for investigating the processes of demyelination and remyelination associated with MS. In our research, we examined the protective and therapeutic effects of betaine in a rat model of MS induced by CPZ. The experimental protocol involved administering 600 mg/kg of CPZ orally for 7 days, followed by 2 weeks with 200 …

Using Acutely Dissociated and Purified Oligodendrocyte Precursor Cells for High-Throughput Drug Screening to Identify Compounds that Promote Oligodendrocyte Differentiation.

Multiple sclerosis (MS) is an autoimmune disease that involves an immune-mediated inflammatory response in the central nervous system and optic nerve resulting in demyelination and neural degeneration, the cause of which is unknown. The adult central nervous system has the capacity to remyelinate axons by generating new oligodendrocytes (OLs). To identify clinical candidate compounds that may promote remyelination, we have developed a high-throughput screening (HTS) assay to identify compounds that promote the differentiation of oligodendrocyte precursor cells (OPCs) into OLs. Using acutely di…

17beta-estradiol protects male mice from cuprizone-induced demyelination and oligodendrocyte loss.

In addition to regulating reproductive functions in the brain and periphery, estrogen has tropic and neuroprotective functions in the central nervous system (CNS). Estrogen administration has been demonstrated to provide protection in several animal models of CNS disorders, including stroke, brain injury, epilepsy, Parkinson's disease, Alzheimer's disease, age-related cognitive decline and multiple sclerosis. Here, we use a model of toxin-induced oligodendrocyte death which results in demyelination, reactive gliosis, recruitment of oligodendrocyte precursor cells and subsequent remyelination t…

Lysosomal cholesteryl ester hydrolysis drives white matter repair by reprogramming microglia into a novel reparative state.

White matter repair relies on microglial clearance of cholesterol-rich myelin debris. Microglia have been reported to predominantly depend o … MB+ microglia displayed context-dependent capacity to digest internalized myelin debris and mediate remyelination, with marked differences between reparable white matter injury and nonregenerative injury induced by white matter stroke (WMS). Transcriptomic profiling identified LAL as a key regulator of the reparative phenotype in GPNMB+ microglia. Independent o …

Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination.

BACKGROUND: Abnormal lipid accumulation has been recognized as a key element of immune dysregulation in microglia whose dysfunction contribu … CPZ) diet for four weeks to induce demyelination in the brain. To examine the effects on subsequent remyelination, the cuprizone diet was switched back to regular chow for an additional two weeks. After treatment, brains were collected and subjected to immunohistochemical and biochemical analyses to assess the myelination status, microglial responses, and their …

New insights in multiple sclerosis pathology.

PURPOSE OF REVIEW: Current concepts suggest that relapse associated worsening as well as progression independent of relapse activity contrib … e progression in MS. Furthermore, the detrimental role of soluble factors for neurons, synapses and remyelination becomes more evident. Combined experimental and human tissue studies revealed detrimental neuronal injury mechanisms triggered by interferon γ. The analysis of MS tissue samples by modern -omic approaches added to the disentangling of the complex in …

Разработка и применение метода ЛК-МС для фармакокинетики и фармакодинамики пероральной терапевтической эффективности нальфурафина.

Множественный склероз (MS) — хроническое аутоиммунное заболевание, характеризующееся обезвоживанием центральной нервной системы, приводящее к сенсорной и моторной дисфункции. Предыдущие исследования показали, что каппа-опиоидный рецептор агонистический налфурафин (Nalf) снижает степень заболеваемости и поощряет ремиилизацию в экспериментальной аутоиммунной энцефаломиелитной (EAE) модели MS. Однако фармакокинетика Нальфа и его оптимальный административный путь к клиническому переводу остаются неизученными. Для изучения фармакокинетики Нальфа и определения эффективной стратегии пероральной доста

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune disease characterized by central nervous system demyelination, leading to sensory and motor dysfunction. Previous studies have demonstrated that the kappa opioid receptor agonist nalfurafine (Nalf) reduces disease severity and promotes remyelination in the experimental autoimmune encephalomyelitis (EAE) model o…

Trem2-deficiency aggravates and accelerates age-related myelin degeneration.

Aging is the greatest known risk factor for most neurodegenerative diseases. Myelin degeneration is an early pathological indicator of these diseases and a normal part of aging; albeit, to a lesser extent. Despite this, little is known about the contribution of age-related myelin degeneration on neurodegenerative disease. Microglia participate in modulating white matter events from demyelination to remyelination, including regulation of (de)myelination by the microglial innate immune receptor triggering receptor expressed on myeloid cells 2 (TREM2). Here, we demonstrate Trem2-deficiency aggrav…

Olfactory ensheathing cells express smooth muscle alpha-actin in vitro and in vivo.

One strategy for spinal cord repair after injury that has moved quickly from the research laboratory to the clinic is the implantation of olfactory ensheathing cells (OECs). These unique glial cells of the olfactory system have been associated with axonal remyelination and regeneration after grafting into spinalized animals. Despite these promising observations, there remains a lack of direct empirical evidence of the exact fate of OECs after intraspinal implantation, in large part because of a surprising paucity of defined biomarkers that unequivocally distinguish these cells from phenotypica…

Expression of myelin-associated glycoprotein isoforms after sciatic nerve crush injury in mice.

The large myelin-associated glycoprotein isoform (L-MAG) protein and small myelin-associated glycoprotein isoform (S-MAG) protein were demon … ed that L-MAG mRNA was characteristically induced at the time of most active myelination, including remyelination in the CNS. We here have shown the expression of L-MAG protein precedes that of S-MAG protein during active remyelination in the PNS. This suggests that it plays an important role in the early stage of myelin formation.

Therapeutic potential of retinoic acid-loaded lipid Nanocapsules in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis.

Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting over 2.5 million people worldwide. Despite available therapies, no current treatment halts disease progression or specifically targets remyelination. Here, we evaluated for the first time the early therapeutic potential of retinoic acid-loaded lipid nanocapsules (LNC RA in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. We first compared intravenous and intranasal administration routes. While transferrin-receptor binding peptide (TfRp)-LNC demonstrated enhanced permeability across an in vitro nasal …

Nucleoside-Analog Reverse-Transcriptase Inhibitors (NRTIs) Against Multiple Sclerosis: Comprehensive Review on a Possible Novel Therapeutic Approach.

To this day, the etiology of multiple sclerosis has yet to be fully comprehended by the scientific community. However, the knowledge on mechanisms leading to the development of this neurodegenerative autoimmune disorder increases daily, along with the development of new disease-modifying treatments. A correlation between Epstein-Barr Virus infection and the disease incidence has recently shed light on possible innovative antiviral therapies. Here, we review the literature on Human Endogenous Retroviral sequences as emerging actors for the impairment of remyelination as a major challenge in dis…

Impact of the Voltage-Gated Calcium Channel Antagonist Nimodipine on the Development of Oligodendrocyte Precursor Cells.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While most of the current treatment strategies focus on immune cell regulation, except for the drug siponimod, there is no therapeutic intervention that primarily aims at neuroprotection and remyelination. Recently, nimodipine showed a beneficial and remyelinating effect in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Nimodipine also positively affected astrocytes, neurons, and mature oligodendrocytes. Here we investigated the effects of nimodipine, an L-type voltage-g…