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Perineurium contributes to axonal damage in acute inflammatory demyelinating polyneuropathy.

OBJECTIVE: To assess if axonal damage in severe acute inflammatory demyelinating polyneuropathy (AIDP) correlates with the appearance of epi … myelinated fibers was preserved in L5 ventral and dorsal roots and reduced in sural nerve. Mild de-remyelination was observed in lumbar roots. In both lumbar nerves and their branches, there were extensive de-remyelination and centrofascicular or wedge-shaped areas with marked loss of large myelinated fibers. Axonal degeneration was the predominant lesion in s …

RXR Gamma Enables Oligodendrocyte Differentiation by Suppressing Sonic Hedgehog Signaling.

Overcoming remyelination failure is one of the main targets in therapeutic strategies for multiple sclerosis. This process requires the differentiation of oligodendrocyte precursor cells (OPCs) to mature myelinating oligodendrocytes (OLs), a process known to be controlled by thyroid hormone, nuclear receptors, and sonic hedgehog (SHH). Retinoid X receptor gamma (RXRg) is one of the nuclear receptors acting as a positive regulator of remyelination, but little is known about its mechanisms of function. Using transcriptomic and pharmacological analysis of primary neural stem cell-derived OPCs, we…

Ремонт тканей в центральной нервной системе: эпигенетическое программирование регуляторных Т клеток.

Регулирующие Т клетки хорошо известны своей иммуномодуляционной ролью, но также их регенеративная функция все чаще признается в различных типах тканей, включая скелетные мышцы, легкие и центральную нервную систему (ЦНС). В CNS Tregs, как было показано, поощряют дифференциацию олигодендроцитов в прекурсорных клетках, и их взаимодействие с микроглией поддерживает стимулирующую регенеративную микроокружную среду в мозгу. Подавляющая функция Tregs в значительной степени зависит от эпигенетической сигнатуры, в частности метилации ДНК, определенной сети связанных с Treg генов, включая FOXP3, CTLA4,

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Regulatory T cells are well known for their immunomodulatory role but also their regenerative function is increasingly recognized across mul … erosis (MS). MS is characterized by chronic neuroinflammation and neurodegeneration associated with remyelination failure. In MS, Treg suppressive function is compromised and epigenetic dysregulation at key Treg loci has been reported. However, the role of those loci in repair is unknown and the methylation status of regenerative genes in MS Tregs has not been …

Эксплуатация на тренировочной мельнице влияет на электрофизиологическую и глиальную иммуноактивность в крысах, покрытых купризонами.

Фон/цели: Демиелинация происходит в различной степени в различных неврологических заболеваниях, таких, как множественный склероз. Физическое упражнение помогает центральным нервным функциям, которые зависят от электрофизиологической и глиальной активности мозга. Неясно, как факторы - т.е. обезвоживание и интерактивность упражнений в мозге. Мы стремились выяснить, происходит ли это взаимодействие во время развития мозга. Методы: Развивающиеся крысы подвергались демиэлизации, вызванной купризоной. Часть этих крыс прокатилась на беговой дорожке в течение пяти недель. После этого времени некоторым

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Background/Objectives: Demyelination occurs to a variable extent in various neurological diseases, such as multiple sclerosis. Physical exer … propagation. Cuprizone reduced APC, MBP, and GFAP immunolabeling and increased Iba1 immunostaining. Remyelination reverted the cuprizone effects. Exercise counteracted the cuprizone-induced changes in GFAP- and Iba1-containing cells but not in MBP- and APC-containing ones. Conclusions: Our data confirmed the effectiveness of the cuprizone demyelination paradigm …

Глюкагон, как пептид1 Агонисты рецепторов в множестве склерозов: терапевтические обещания, проблемы и будущие направления.

ВВЕДЕНИЕ: В настоящем обзоре оценивается потенциал глюкагона, похожего на пептида1 агонисты рецептора (GLP-1RAs) - впервые разработанные для типа 2 диабет, который впоследствии был утвержден для регулирования хронического веса и дополнительных показателей, которые должны быть использованы в качестве нейрозащитных и ремиелионирующих методов лечения при множественном склерозе (МС). Мы обобщаем возникающие доклинические и ранние клинические данные, выявляем практические препятствия на пути перевода и намечаем направления будущих исследований.В экспериментальных аутоиммунных энцефаломиэлитах и мыш

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INTRODUCTION: This review evaluates the potential of glucagon‑like peptide‑1 receptor agonists (GLP‑1RAs) - first developed for type 2 diabe … eserve axonal integrity, suppress microglial and astrocytic activation, and, in some cases, promote remyelination. Early observational data in people with MS suggest GLP-1RAs are well tolerated, provide expected metabolic benefits, and do not exacerbate disease activity. Moreover, signals of reduced neurological impairment and lower dementia incidence in broade …

Демиелинция производит сдвиг в населении кортикальных нейронов, которые синапсируют с каллосальными олигодендроцитными клетками.

Клетки потомства олигодендроцитов (ОРК) получают синаптическое воздействие от различных нейронов в мозгу развивающихся и взрослых. Понимание того, меняются ли нейронные популяции, которые синапируют с OPC в здоровом мозге в результате обезвоживания и/или ремиэлирования, может способствовать совершенствованию стратегий нейрозащиты или миелинового ремонта, разрабатываемых для демиелинизирующих заболеваний, таких, как множественный склероз. Чтобы изучить эту возможность, мы использовали трансгенную технологию крелокса, чтобы облегчить инфекцию ОПС модифицированным вирусом бешенства, что позволяет

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Oligodendrocyte progenitor cells (OPCs) receive synaptic input from a diverse range of neurons in the developing and adult brain. Understanding whether the neuronal populations that synapse with OPCs in the healthy brain is altered by demyelination and/or remyelination may support the advancement of neuroprotective or myelin repair strategies being developed…

The comparative effects of bone marrow mesenchymal stem cells and supernatant transplantation on demyelination and inflammation in cuprizone model.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) with inflammation and immune dysfunction. OBJECTIVES: We compared the remyelination and immunomodulation properties of mesenchymal stem cells (MSCs) with their conditioned medium (CM) in the cuprizone model. METHODS: Twenty-four C57BL/ 6 mice were divided into four groups. After cuprizone demyelination, MSCs and their CM were injected into the right lateral ventricle of mice. The expression level of IL-1β, TNF-α, and BDNF genes was evaluated using the qRT-PCR. APC antibody was used to a…

Emerging concepts in the treatment of optic neuritis: mesenchymal stem cell-derived extracellular vesicles.

BACKGROUND: Optic neuritis (ON) is frequently encountered in multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein associated disease, and other systemic autoimmune disorders. The hallmarks are an abnormal optic nerve and inflammatory demyelination; episodes of optic neuritis tend to be recurrent, and particularly for neuromyelitis optica spectrum disorder, may result in permanent vision loss. MAIN BODY: Mesenchymal stem cell (MSC) therapy is a promising approach that results in remyelination, neuroprotection of axons, and has demonstrated succes…

Assessing the anterior visual pathway in optic neuritis: recent experimental and clinical aspects.

PURPOSE OF REVIEW: Multiple sclerosis (MS) and related autoimmune disorders of the central nervous system such as neuromyelitis optica spectrum disorders (NMOSD) are characterized by chronic disability resulting from autoimmune neuroinflammation, with demyelination, astrocyte damage, impaired axonal transmission and neuroaxonal loss. Novel therapeutics stopping or reversing the progression of disability are still urgently warranted. This review addresses research on optic neuritis in preclinical experimental models and their translation to clinical trials. RECENT FINDINGS: Optic neuritis can

Theiler's murine encephalomyelitis virus preferentially infects immature stages of the murine oligodendrocyte precursor cell line BO-1 and blocks oligodendrocytic differentiation in vitro.

Theiler's murine encephalomyelitis virus (TMEV)-induced demyelination is an important animal model for multiple sclerosis. The presence of oligodendrocyte precursor cells (OPCs) within demyelinated lesions together with the limited extent of remyelination has raised the question of how OPCs are affected by TMEV. It is well established that oligodendrocytes, astrocytes and microglia are targets during the chronic phase of the disease. However, whether TMEV infection interferes with the capacity of OPCs to generate oligodendrocytes has remained unclear. In the present study, a bipotential murine…

Ultrastructural observations on the progress of nerve degeneration and regeneration at the suture site following vagal-hypoglossal nerve coaptation in cats.

Nerve degeneration and regeneration have been investigated at the suture site following proximal-to-distal vagal-hypoglossal nerve coaptatio … lay a key role in navigating the regenerating axons to their newly acquired target organ at 22 dpo. Remyelination of axons was not observed till 46 dpo. Compared with the rapid axonal reaction in other models of nerve injury, the degeneration process in VHC was protracted and, furthermore, regeneration and remyelination were delayed. The subtle remodeling of th …

Roles of meltrin-beta/ADAM19 in progression of Schwann cell differentiation and myelination during sciatic nerve regeneration.

Remyelination is an important aspect of nerve regeneration after nerve injury, but the underlying mechanisms are not fully understood. Here, we show that meltrin-beta (ADAM19), a member of the ADAM (a disintegrin and metalloprotease) family, plays crucial roles in nerve regeneration after a crush injury to the sciatic nerves. The expression of meltrin-beta was up-regulated in neurons after the crush injury. Morphometrical analysis revealed a delay in remyelination in meltrin-beta-deficient nerves, whereas no significant defects were observed in their axon elongation. The activation of Krox-20,…

[A family of hereditary motor and sensory neuropathy type I with a new type of myelin P0 mutation].

A 26-year-old man had complaints of insidiously progressive muscle weakness of the legs, worse in the right leg than in the left. Slight to … ular biopsy of the right sural nerve was performed. The myelinated fibers showing segmental de- and remyelination were frequently found in teased fiber preparations. Both demyelinated and remyelinated axons and onion-bulbs were frequently observed by light and electron microscopy in the Epon-embedded sections. Based on the neurological examinations and nerve co …

Sural nerve biopsy findings in leprosy: a qualitative and quantitative light and electron microscope study in 4 treated cases of the lepromatous spectrum.

Reports on biopsy findings in multifascicular nerves in lepromatous leprosy (LL) are rare and detailed morphometrical data are not available. In a case of early LL with normal electrodiagnostic findings in sural nerve, the present study revealed marked segmental de- and remyelination concomitant with the sequelae of considerable Wallerian degeneration of preferentially small myelinated fibers (MF) in spite of a normal number/nerve and density/mm2. Segmental de- and remyelination of several consecutive internodes in teased fibers suggests continuous bacterial spread via Schwann cells. In 2 more…

Human diabetic endoneurial sorbitol, fructose, and myo-inositol related to sural nerve morphometry.

Fascicles of the sural nerve from each of 20 diabetic patients, mostly with maturity-onset diabetes, were studied by biochemical and patholo … of neuropathy, a higher than normal frequency of teased fibers showing segmental demyelination and remyelination was found. Untreated diabetics with symptomatic neuropathy showed two kinds of abnormalities: fibers with segmental demyelination and remyelination and fibers undergoing axonal degeneration. In treated diabetics, who often had longstanding neuropath …

Микроглиа регулирует расчистку миелин и метаболизм холестерина после демиелинации с помощью интерферона регулирующего коэффициента 5.

Регулирующий фактор интерферона 5 (IRF5) — это фактор транскрипции, который играет определенную роль в организации врожденной иммунной реакции, особенно в ответ на вирусные инфекции. В частности, IRF5 был определен как ген микроглийного риска, связанный с множественным склерозом (MS), однако его конкретная роль в патогенезе MS остается неясной. С помощью ирф5-/- мышей наше исследование обнаруживает неканоническую функцию IRF5 в восстановлении MS. Ирф5-/- мыши продемонстрировали повышенный ущерб в экспериментальной модели аутоиммунной энцефаломиелита (EAE) и продемонстрировали неисправный набор

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Interferon regulatory factor 5 (IRF5) is a transcription factor that plays a role in orchestrating innate immune responses, particularly in … rol esters, and cholesterol crystals within demyelinating lesions. This abnormal buildup can hinder remyelination processes. Importantly, treatments that promote cholesterol transport were found to reduce lipid droplet accumulation and mitigate the exacerbated damage in Irf5-/- mice with EAE. Altogether, our study identified the antiviral transcription factor I …

Vitamin C regulates Schwann cell myelination by promoting DNA demethylation of pro-myelinating genes.

Ascorbic acid (vitamin C) is critical for Schwann cells to myelinate peripheral nerve axons during development and remyelination after injury. However, its exact mechanism remains elusive. Vitamin C is a dietary nutrient that was recently discovered to promote active DNA demethylation. Schwann cell myelination is characterized by global DNA demethylation in vivo and may therefore be regulated by vitamin C. We found that vitamin C induces a massive transcriptomic shift (n = 3,848 genes) in primary cultured Schwann cells while simultaneously producing a global increase in genomic 5-hydroxymethyl…

Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death.

Seeking for effective drugs which are beneficial to facilitating axonal regrowth and elongation after peripheral nerve injury (PNI) has gain … atic crush injury, manifesting as persistently improved motor and sensory function, enhanced axonal remyelination and regrowth and accelerated Schwann cells (SCs) proliferation. Furthermore, local FGF21 application attenuated the excessive activation of oxidative stress, which was accompanied with the activation of nuclear factor erythroid-2-related factor 2 (N …

Chronic demyelinating neuropathy and intra-axonal polyglucosan bodies.

In this study we evaluated the relationship between polyglucosan bodies and peripheral nerve lesions. The biopsied sural nerve from a patient with late-onset chronic sensori-motor neuropathy showed many intra-axonal polyglucosan bodies and segmental demyelination/remyelination. The formation of Schwann cell hyperplasia around the demyelinated axons was found at the sites of polyglucosan bodies. These findings suggest that demyelinating neuropathy is a part of the spectrum of the diseases characterized by the accumulation of polyglucosan bodies within cellular compartments.

Leukotriene inhibitors in multiple sclerosis: a systematic review of animal studies.

Current disease-modifying therapies for multiple sclerosis (MS) primarily target adaptive immunity but often fail to halt neurodegeneration … ed central nervous system (CNS) delivery using engineered exosomes appeared to enhance the observed remyelination effects. Leukotriene inhibition may exert pleiotropic effects across both peripheral immune responses and the CNS microenvironment. Although these mechanistic observations provide biological plausibility for further investigation of these agents as …