Результаты поиска

Fibronectin inhibition restores myelination in endothelial TNFR2-dependent nonremitting experimental autoimmune encephalomyelitis.

In multiple sclerosis (MS), spontaneous remyelination occurs in early disease; however, this process becomes inefficient over time, resulting in sustained neurodegeneration and clinical deterioration. It is known that global tumor necrosis factor receptor 2 (TNFR2) deletion in experimental autoimmune encephalomyelitis (EAE), the murine MS model, causes a severe nonremitting disease; however, the underlying mechanism is poorly understood. Here, through bulk and single nucleus RNA sequencing, we identify endothelial TNFR2 deletion as the driver of nonremitting disease, as it is sufficient to dri…

Cortical demyelination is prominent in the murine cuprizone model and is strain-dependent.

The cuprizone model of toxic demyelination in the central nervous system is commonly used to investigate the pathobiology of remyelination in the corpus callosum. However, in human demyelinating diseases such as multiple sclerosis, recent evidence indicates a considerable amount of cortical demyelination in addition to white matter damage. Therefore, we have investigated cortical demyelination in the murine cuprizone model. To induce demyelination, C57BL/6 mice were challenged with 0.2% cuprizone feeding for 6 weeks followed by a recovery phase of 6 weeks with a cuprizone-free diet. In additio…

In Vivo Optical Imaging of Myelination Events in a Myelin Basic Protein Promoter-Driven Luciferase Transgenic Mouse Model.

The compact myelin sheath is important for axonal function, and its loss can lead to neuronal cell death and irreversible functional deficit … P promoter. In vivo bioluminescence imaging can be used to visualize and quantify demyelination and remyelination at the transcriptional level, noninvasively, and in real time. Transgenic mice were assessed in the cuprizone-induced model of demyelination, and luciferase activity highly correlated with demyelination and remyelination events as confirmed by both …

The effects of normal aging on myelinated nerve fibers in monkey central nervous system.

The effects of aging on myelinated nerve fibers of the central nervous system are complex. Many myelinated nerve fibers in white matter dege … ent oligodendrocyte, and that the production of increased numbers of internodes as a consequence of remyelination requires additional oligodendrocytes. Whether there is a turnover of oligodendrocytes during life has not been studied in primates, but it has been established that over the life span of the monkey, there is a substantial increase in the numbers of …

Нацеливание на астроцитический CLC2 (CLCN2) восстанавливает регенерацию миелина посредством ингибиции SPP1/CD44 сигнализирующего пути в лейкоэнцефалопатии.

Аккумулирование миелиновых повреждений и поврежденное ремиелионирование являются центральными патологическими особенностями лейкоэнцефалопатии, включая множественный склероз и болезнь Александра, где астроциты играют важную роль в поддержании гомеостаза центральной нервной системы и посредничестве взаимодействия астроцита-олигодендроцитов. Хлорид Ion Channel 2 (CIC-2), кодируемый CLCN2, функционально выражается в астроцитах и, вероятно, имеет решающее значение для целостности белого вещества; однако его точные роли и взаимодействие остаются неясными. Уточнение механизмов, с помощью которых аст

Совпадение в аннотации оригинала
Accumulating myelin damage and impaired remyelination are central pathological features of leukoencephalopathies, including Multiple Sclerosis and Alexander Disease, where astrocytes play essential roles in maintaining central nervous system homeostasis and mediating astrocyte-oligodendrocyte interactions. Chloride Ion Channel 2 (ClC-2), encoded by CLCN2, is…

TREM2 mediates physical exercise-promoted neural functional recovery in rats with ischemic stroke via microglia-promoted white matter repair.

BACKGROUND: The repair of white matter injury is of significant importance for functional recovery after ischemic stroke, and the up-regulation of triggering receptors expressed on myeloid cells 2 (TREM2) after ischemic stroke is neuroprotective and implicated in remyelination. However, the lack of effective therapies calls for the need to investigate the regenerative process of remyelination and the role of rehabilitation therapy. This study sought to investigate whether and how moderate physical exercise (PE) promotes oligodendrogenesis and remyelination in rats with transient middle cerebra…

Oligodendroglial ring finger protein Rnf43 is an essential injury-specific regulator of oligodendrocyte maturation.

Oligodendrocyte (OL) maturation arrest in human white matter injury contributes significantly to the failure of endogenous remyelination in multiple sclerosis (MS) and newborn brain injuries such as hypoxic ischemic encephalopathy (HIE) that cause cerebral palsy. In this study, we identify an oligodendroglial-intrinsic factor that controls OL maturation specifically in the setting of injury. We find a requirement for the ring finger protein Rnf43 not in normal development but in neonatal hypoxic injury and remyelination in the adult mammalian CNS. Rnf43, but not the related Znrf3, is potently …

Acute and chronic demyelinated CNS lesions exhibit opposite elastic properties.

Increased deposition of extracellular matrix (ECM) is a known inhibitor of axonal regrowth and remyelination. Recent in vitro studies have demonstrated that oligodendrocyte differentiation is impacted by the physical properties of the ECM. However, characterization of the mechanical properties of the healthy and injured CNS myelin is challenging, and has largely relied on non-invasive, low-resolution methods. To address this, we have employed atomic force microscopy to perform micro-indentation measurements of demyelinated tissue at cellular scale. Analysis of mouse and human demyelinated brai…

Сокращение холестерина меняет биофизические свойства отремонтированного миелина.

Миелиновая оболочка — это насыщенная липидом мембрана, которая покрывает аксоны и необходима для здорового и эффективного трансдукции сигнала. Миелин страдает неврологическими заболеваниями, как и множественный склероз, но ремиелионация может происходить в результате действия олигодендроцитов-прекурсоров (ОРК), которые проводят различие с зрелыми олигодендроцитами, которые обворачивают аксоны для создания восстановленного миелина. В этом исследовании использовалась генетическая модель обезвоживания мыши, которая содержит почти полное обезвоживание, за которым следует сильное обезвоживание в мо

Совпадение в аннотации оригинала
The myelin sheath is a lipid-rich membrane that ensheathes axons and is required for healthy and efficient signal transduction. Myelin is damaged in neurological diseases like multiple sclerosis, but remyelination can occur through the action of oligodendrocyte precursor cells (OPCs), which differentiate into mature oligodendrocytes that wrap axons to form r…

Time is myelin: early cortical myelin repair prevents atrophy and clinical progression in multiple sclerosis.

Cortical myelin loss and repair in multiple sclerosis (MS) have been explored in neuropathological studies, but the impact of these processes on neurodegeneration and the irreversible clinical progression of the disease remains unknown. Here, we evaluated in vivo cortical demyelination and remyelination in a large cohort of people with all clinical phenotypes of MS followed up for 5 years using magnetization transfer imaging (MTI), a technique that has been shown to be sensitive to myelin content changes in the cortex. We investigated 140 people with MS (37 clinically isolated syndrome, 71 rel…

Magnetization transfer ratio recovery in new lesions decreases during adolescence in pediatric-onset multiple sclerosis patients.

Children and adolescents diagnosed with multiple sclerosis rarely accrue physical disability early in their disease. This could be explained by greater remyelination in children, a capacity that may be lost in adolescence or early adulthood. Magnetization transfer ratio (MTR) MRI can be used to quantify changes in myelin in MS. We used serial MTR imaging and longitudinal random effects analysis to quantify recovery of MTR in acute lesions and to evaluate MTR changes in normal-appearing tissue in 19 adolescent MS patients. Our objective was to determine whether younger adolescents have a greate…

Transplanted human iPSC-derived vascular endothelial cells promote functional recovery by recruitment of regulatory T cells to ischemic white matter in the brain.

BACKGROUND: Ischemic stroke in white matter of the brain induces not only demyelination, but also neuroinflammation. Peripheral T lymphocyte … detect the activated microglia and macrophages, T cells, Tregs, and oligodendrocyte lineage cells. Remyelination was examined by Luxol fast blue staining. RESULTS: iVEC transplantation reduced ED-1+ inflammatory cells and CD4+ T cells, while increased Tregs in the white matter infarct. Treatment of the animals with FTY720 suppressed neuroinflammation and redu …

Myelin repair is accelerated by inactivating CXCR2 on nonhematopoietic cells.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS and remyelination in MS ultimately fails. Although strategies to promote myelin repair are eagerly sought, mechanisms underlying remyelination in vivo have been elusive. CXCR2 is expressed on neutrophils and oligodendrocyte lineage cells in the CNS. CXCR2-positive neutrophils facilitate inflammatory demyelination in demyelination models such as experimental autoimmune encephalomyelitis (EAE) and cuprizone intoxication. Systemic injection of a small molecule CXCR2 antagonist at the onset of EAE decreased demyelinated le…

Lack of astrocytes hinders parenchymal oligodendrocyte precursor cells from reaching a myelinating state in osmolyte-induced demyelination.

Demyelinated lesions in human pons observed after osmotic shifts in serum have been referred to as central pontine myelinolysis (CPM). Astrocytic damage, which is prominent in neuroinflammatory diseases like neuromyelitis optica (NMO) and multiple sclerosis (MS), is considered the primary event during formation of CPM lesions. Although more data on the effects of astrocyte-derived factors on oligodendrocyte precursor cells (OPCs) and remyelination are emerging, still little is known about remyelination of lesions with primary astrocytic loss. In autopsy tissue from patients with CPM as well as…

Spatial transcriptomics reveal heterogeneous cell‒cell interactions among brain regions in cuprizone model consistent with multiple sclerosis lesions.

The cuprizone (CPZ) model is widely used for modeling demyelination in multiple sclerosis (MS) and for testing potential remyelination therapies. To better understand the underlying pathology of the CPZ model and evaluate its translatability, we integrated single-cell and spatial transcriptomics (ST) to investigate spatial cellular and molecular interactions during de- and remyelination in multiple brain regions. ST revealed global demyelination and neuroinflammation in the brain beyond the corpus callosum (CC), with region-specific differences. We identified oligodendroglia and microglia as t…

Dynamics of reactive astrocytes fosters tissue regeneration after cuprizone-induced demyelination.

Demyelination in the central nervous system (CNS) is a hallmark of many neurodegenerative diseases such as multiple sclerosis (MS) and others. Here, we studied astrocytes during de- and remyelination in the cuprizone mouse model. To this end, we exploited the ribosomal tagging (RiboTag) technology that is based on Cre-mediated cell type-selective HA-tagging of ribosomes. Analyses were performed in the corpus callosum of GFAP-Cre+/- Rpl22HA/wt mice 5 weeks after cuprizone feeding, at the peak of demyelination, and 0.5 and 2 weeks after cuprizone withdrawal, when remyelination and tissue repair …

Carnosol and melatonin co-treatment attenuates neuroinflammation and oxidative stress in experimental autoimmune encephalomyelitis.

INTRODUCTION: Neurodegenerative diseases such as multiple sclerosis (MS) involve neuronal loss and functional impairment driven by inflammation and oxidative stress. Carnosol and melatonin are recognized for their anti-oxidative properties and potential to support remyelination. This study assessed the combined therapeutic effect of Carnosol and melatonin in the experimental autoimmune encephalomyelitis (EAE) model. MATERIALS AND METHODS: EAE was induced in 28 female C57BL/6 mice, which were divided into four groups: Control, Carnosol (50 mg/kg), melatonin (10 mg/kg), and combination treatmen…

Combination effects of mesenchymal stem cells transplantation and anodal transcranial direct current stimulation on a cuprizone-induced mouse model of multiple sclerosis.

Multiple sclerosis (MS) has no absolute treatment, and researchers are still exploring to introduce promising therapy for MS. Transcranial direct current stimulation (tDCS), is a safe, non-invasive procedure for brain stimulating which can enhance working memory, cognitive neurohabitation and motor recovery. Here, we evaluated the effects of tDCS treatment and Mesenchymal stem cells (MSCs) transplantation on remyelination ability of a Cuprizone (CPZ)-induced demyelination mouse model. tDCS significantly increased the motor coordination and balance abilities in CPZ + tDCS and CPZ + tDCS + MSCs …

A novel model to measure the regenerative potential of the peripheral nervous system after experimental immunological demyelination.

BACKGROUND: Immunological demyelination is a proposed strategy to improve nerve regeneration in the peripheral nervous system. To investigat … t proteins plus antibodies to galactocerebroside resulted in demyelination followed by Schwann cell remyelination. At 3 days after injection, peripheral nerve demyelination and Schwann cell proliferation were evident. Maximum demyelination was seen at 7 days; however, Schwann cell proliferation and remyelination peaked at 14 days after injection. CONCLUSIONS: …

IFN-γ-Responsive Microglia-Derived Extracellular Vesicles Impair White Matter Repair After Stroke Through a miR-9-5p/NEDD4-Dependent Mechanism.

Promoting white matter repair is crucial for functional recovery after ischemic stroke. Our previous study has identified an IFN-γ-responsiv … tic interventions including miR-9-5p knockdown in IFN-γ EVs or NEDD4 overexpression in OPCs restore remyelination and functional recovery. Our findings demonstrate that IFN-γ EVs act as negative regulators of OPCs differentiation and remyelination following ischemic stroke via miR-9-5p/NEDD4 pathway. Targeting this signaling axis may represent a novel therapeut …