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Whole Mount Immunostaining on Mouse Sciatic Nerves to Visualize Events of Peripheral Nerve Regeneration.

Injury to the peripheral nervous system triggers a series of well-defined events within both neurons and the Schwann cells to allow efficient axonal regeneration, remyelination, and functional repair. The study of these events has previously been done using sections of nerve material to analyze axonal regrowth, cell migration, and immune cell infiltration following injury. This approach, however, has the obvious disadvantage that it is not possible to follow, for instance, the path of regenerating axons in three dimensions within the nerve trunk or the nerve bridge. In order to provide a fulle…

[Development and regeneration of oligodendrocytes: therapeutic perspectives in demyelinating diseases].

The function of the central nervous system (CNS) is in great part depending on glial cells as, for instance, radial glial cells give rise to … h precursors can be isolated from human brain and persist in the adult CNS, allowing some degree of remyelination in the course of a demyelinating disease caused by an infectious agent or inflammation such as multiple sclerosis (MS). These remyelinating cells can recapitulate some molecular events of myelination while new OPs are generated by neural stem cells …

FOXP3+ Macrophage-Derived Amphiregulin способствует ремонту белых материалов экспериментального аутоиммунного энцефаломиэлита.

Множественный склероз (MS) характеризуется эпизодами подстрекательского обезвоживания, за которым следуют различные степени ремилеляции. Ключевую роль в обоих процессах играют макроматериалы. Понимание того, как макрофаги изменяют свою пластичность, чтобы облегчить воспоминание в MS, обладает значительным терапевтическим потенциалом, однако этот механизм по-прежнему недостаточно изучен. В этом исследовании мы показываем, что пищеварение миелинового мусора макрофагами приводит к активации сигнала FOXP3, который вызывает прорегенеративный фенотип. В частности, мы создали специфическую для макроф

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is characterized by episodes of inflammatory demyelination followed by varying degrees of remyelination. Macrophages play a pivotal role in both processes. Understanding how macrophages modulate their plasticity to facilitate remyelination in MS holds significant therapeutic potential, yet this mechanism remains poorly understood. In …

Oligodendrocyte и Myelin патофизиология в мультиклерозе.

Множественный склероз (MS) — хроническое аутоиммунное и прогрессивное нейродегенеративное заболевание центральной нервной системы (CNS), имеющее весьма изменчивое клиническое проявление и курс. MS преследует главным образом миелина и олигодендроглию; однако все глиальные клетки и нейроны начинают участвовать в патологии. Таким образом, воспаление, которое широко считается инициированным в периферии, расширяется через CNS, причем астроциты и микроглиа попадают в активированное состояние не только вокруг и внутри повреждений, но и широко распространены. В этой главе будут подчеркнуты патофизиоло

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune and progressive neurodegenerative disease of the central nervous system (CNS) that has a hig … sion of CNS atrophy and symptoms. Finally, exploiting paradigms of oligodendrocyte repopulation and remyelination will definitively contribute to devising treatments for tissue repair and halting MS course. This chapter aims at summarizing the state of the art in all these experimental developments including the available clinical therapies and the current clin …

Myelin repair in Alzheimer's disease: a review of biological pathways and potential therapeutics.

This literature review investigates the significant overlap between myelin-repair signaling pathways and pathways known to contribute to hallmark pathologies of Alzheimer's disease (AD). We discuss previously investigated therapeutic targets of amyloid, tau, and ApoE, as well as other potential therapeutic targets that have been empirically shown to contribute to both remyelination and progression of AD. Current evidence shows that there are multiple AD-relevant pathways which overlap significantly with remyelination and myelin repair through the encouragement of oligodendrocyte proliferation,…

Выборочное ингибирование TLR2 стимулирует созревание олигодендроглиевых клеток потомства до олигодендроцитов.

Важно описать новые технологии для преодоления барьера и поощрения ремиелионации, поскольку многие аксоны остаются демиелиномированными в CNS пациентов с множественным склерозом (MS). Недавние исследования показывают, что LR2 является негативным регулятором созревания олигодендроглиевых клеток потомства (OPC) до олигодендроцитов (OLs) и что TLR2 присутствует в хронических повреждениях MS человека. Однако до недавнего времени не существовало конкретного ингибитора TLR2. Поэтому мы создали пептид, соответствующий TLR2-interacting Домена MyD88 (TIDM), которая конкретно препятствует TLR2, но не др

Совпадение в аннотации оригинала
It is important to describe new technologies for overcoming the barrier and promoting remyelination because many axons remain demyelinated in the CNS of multiple sclerosis (MS) patients. Recent studies indicate that LR2 is a negative regulator of maturation of oligodendroglial progenitor cells (OPCs) to oligodendrocytes (OLs) and that TLR2 is present in huma…

The role of myelin in neurodegeneration: implications for drug targets and neuroprotection strategies.

Myelination of axons in the central nervous system offers numerous advantages, including decreased energy expenditure for signal transmissio … ary and secondary degeneration is also of interest in the exploration of strategies and targets for remyelination, including the use of anti-inflammatory molecules or nanoparticles to deliver drugs. Although the use of these methods in animal models of diseases have shown to be effective in promoting remyelination, very few clinical trials in patients have met …

An update on combination therapies for multiple sclerosis: where are we now?

INTRODUCTION: In theory, combination of two agents, which are suboptimal when given individually, may result in a significant increase in th … ty or worsening, amelioration of adverse effects, and treatment of relapses, and trials to increase remyelination. EXPERT OPINION: Combination of two platform therapies (Interferon-beta or glatiramer acetate) was without additional effect. Clinical trials with add-on, often applying repurposed drugs (e.g. simvastatin, atorvastatin, minocycline, estriol, cyclop …

Quetiapine has an additive effect to triiodothyronine in inducing differentiation of oligodendrocyte precursor cells through induction of cholesterol biosynthesis.

Multiple sclerosis (MS) is characterized by demyelinated lesions in the central nervous system. Destruction of myelin and secondary damage t … ied at the site of lesions, even in adults. Their presence suggests the possibility that endogenous remyelination without transplantation of donor stem cells may be a mechanism for myelin repair in MS. Strategies to develop novel therapies have focused on induction of signaling pathways that stimulate OPCs to mature into myelin-producing oligodendrocytes that c …

The sphingosine 1-phosphate receptor agonist FTY720 is neuroprotective after cuprizone-induced CNS demyelination.

BACKGROUND AND PURPOSE: Modulation of the sphingosine 1-phosphate receptor is an approved treatment for relapsing multiple sclerosis because of its anti-inflammatory effect of retaining lymphocytes within the lymph nodes. Here, we evaluated the potential of an agonist at this receptor, FTY720 (fingolimod), to activate the promyelinating pathways within the brain to encourage remyelination and neuroprotection. EXPERIMENTAL APPROACH: In this study, we used the cuprizone model in male C57BL/6 mice and tested the promyelinating and neuroprotective effects of FTY720 after acute and chronic toxin-i…

Age-related Changes in the Global DNA Methylation Profile of Oligodendrocyte Progenitor Cells Derived from Rat Spinal Cords.

Demyelination of axons plays an important role in the pathology of many spinal cord diseases and injuries. Remyelination in demyelinated lesions is primarily performed by oligodendrocyte progenitor cells (OPCs), which generate oligodendrocytes in the developing and mature central nervous system. The efficiency of remyelination decreases with age. Many reports suggest that this decline in remyelination results from impaired OPC recruitment and differentiation during aging. Of the various molecular mechanisms involved in aging, changes in epigenetic modifications have received particular attenti…

Naturally occurring antibodies as therapeutics for neurologic disease: can human monoclonal IgMs replace the limited resource IVIG?

Naturally occurring autoantibodies (NAbs) are common in normal humans. The majority of NAbs are IgMs, but a small proportion are IgGs. There … er doses than IVIG. Our own studies in a model of MS show that polyclonal human IgM promotes better remyelination than IVIG and that monoclonal IgMs promote greater remyelination than monoclonal IgGs containing identical variable region sequences. We propose that this difference is due to the ability of IgM to cross link cell surface antigens better than IgGs a …

GPCR-Driven Muscarinic M1 and Histamine H1 Receptor Signaling Converging on the PI3K/Akt/mTOR Pathway: Functional Integration in Neuroinflammation and Myelin Repair in Multiple Sclerosis.

Multiple sclerosis is a chronic immune-mediated neurodegenerative disorder characterized by inflammation, demyelination, axonal injury, and progressive neurological disability. Although current disease-modifying therapies effectively reduce relapse frequency and peripheral immune activation, they provide limited protection against long-term neurodegeneration and remyelination failure. Emerging evidence suggests that neurotransmitter receptor-linked intracellular signaling pathways play crucial roles in regulating neuroinflammation, glial function, and neuronal survival. This review comprehensi…

Interleukin-1beta promotes repair of the CNS.

Interleukin-1beta (IL-1beta) is a proinflammatory cytokine associated with the pathophysiology of demyelinating disorders such as multiple sclerosis and viral infections of the CNS. However, we demonstrate here that IL-1beta appears to promote remyelination in the adult CNS. In IL-1beta(-/-) mice, acute demyelination progressed similarly to wild-type mice and showed parallel mature oligodendrocyte depletion, microglia-macrophage accumulation, and the appearance of oligodendrocyte precursors. In contrast, IL-1beta(-/-) mice failed to remyelinate properly, and this appeared to correlate with a l…

Neuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice.

Astrocyte-derived cholesterol supports brain cells under physiological conditions. However, in demyelinating lesions, astrocytes downregulate cholesterol synthesis, and the cholesterol that is essential for remyelination has to originate from other cellular sources. Here, we show that repair following acute versus chronic demyelination involves distinct processes. In particular, in chronic myelin disease, when recycling of lipids is often defective, de novo neuronal cholesterol synthesis is critical for regeneration. By gene expression profiling, genetic loss-of-function experiments, and compr…

Маркеры повреждения аксона в крови и тканях, вызванные острым и хроническим обезвоживанием.

Нейроаксональная травма является одним из основных факторов необратимой инвалидности в условиях демиелионации. Точная оценка связи между демиэлированием и аксонной патологией имеет решающее значение для оценки и разработки эффективных терапевтических подходов. Измерение световой цепи нейрофильтрации (NfL) в крови может, вероятно, позволить продольный мониторинг нейроаксональной травмы при "едином белке разрешения" с высокой патологической спецификой. Здесь мы демонстрируем прочную связь между кровью и тканями, основанными на NfL, оценкой нейроаксональных повреждений и серьезностью подстрекател

Совпадение в аннотации оригинала
Neuroaxonal injury is a major driver of irreversible disability in demyelinating conditions. Accurate assessment of the association between … he same NfL epitopes. In addition, we validate the longitudinal NfL dynamics in relation to de- and remyelination in an inducible genetic model of inflammatory-independent myelin loss. Through inducible knockout of myelin regulatory factor (Myrf) in proteolipid protein (PLP) expressing cells in Myrffl/fl PLP1-CreERT (MyrfΔiPLP) mice, serum NfL peaked at the tim …

Подпорное кортикальное обезвоживание в множестве склероза: систематический обзор частоты, патологии и клинического разнообразия.

Фон. Традиционное понимание множественного склероза (MS) было сосредоточено на рассеянных повреждениях фокусных белых веществ в центральной нервной системе. Однако недавние исследования привлекли внимание к повреждениям кортикальной серой материи, связанным с MS. Цель этого систематического обзора заключается в всестороннем изучении патологических и клинических аспектов подмиелианации в коре головного мозга пациентов с MS, в устранении и устранении существующих противоречий в литературе. В соответствии с руководящими принципами, содержащимися в " Предпочтенном " докладе по систематич

Совпадение в аннотации оригинала
Background- The traditional understanding of multiple sclerosis (MS) has focused on scattered focal white matter lesions within the central … ubpial region. While the cortical region is generally believed to possess significant potential for remyelination, subpial cortical demyelination has been observed to alter the oligodendroglial population in the cerebral cortex, posing obstacles to remyelination. In conclusion, a collaboration of immune structures and mediators may result in subpial cortical de …

Recombinant Erythropoietin Induces Oligodendrocyte Progenitor Cell Proliferation After Traumatic Brain Injury and Delayed Hypoxemia.

Traumatic brain injury (TBI) can result in axonal loss and demyelination, leading to persistent damage in the white matter. Demyelinated axons are vulnerable to pathologies related to an abnormal myelin structure that expose neurons to further damage. Oligodendrocyte progenitor cells (OPCs) mediate remyelination after recruitment to the injury site. Often this process is inefficient due to inadequate OPC proliferation. To date, no effective treatments are currently available to stimulate OPC proliferation in TBI. Recombinant human erythropoietin (rhEPO) is a pleiotropic neuroprotective cytokin…

Basic fibroblast growth factor potentiates myelin repair following induction of experimental demyelination in adult mouse optic chiasm and nerves.

Induction of demyelination in the central nervous system induce the oligodendrocyte progenitors to proliferate, migrate, and differentiate for restoring new myelin sheathes around demyelinated axons. Factors which increase the response of endogenous progenitor cells could be used to improve remyelination. In the current study, the effect of bFGF on lysolecithin-induced demyelination and remyelination processes in mouse optic chiasm and nerves was investigated. Lysolecithin was injected into the optic chiasm of Balb/C mice. Two groups of animals received doses of bFGF (1 or 5 ng/kg i.p.) just b…

Nerve growth factor signaling of p75 induces differentiation and ceramide-mediated apoptosis in Schwann cells cultured from degenerating nerves.

In peripheral nerve regeneration or remyelination, immature Schwann cells expressing p75(NTR) play cardinal roles in the support and regeneration of axons (Griffin JW, Hoffman PN. Peripheral Neuropathy 361-376, 1993). Only one of four to six Schwann cells participate in remyelination of damaged or regenerating axons. The rest of the cells, or supernumerary Schwann cells, show severe atrophy and gradually decrease in number, reestablishing a 1:1 axon-Schwann cell relationship (Said G, Duckett S. Acta Neuropathol (Berl) 53:173-179, 1981). Recent reports demonstrated that severely atrophied super…