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G Protein-Coupled Receptor Signaling in CNS (Re)Myelination.

Loss of function in oligodendroglial cells is a pathological hallmark of demyelinating and neurodegenerative diseases. A significant pool of oligodendrocyte precursor cells is maintained in the adult brain following developmental myelination. This population of cells provides plasticity to the myelin network that is crucial for healthy brain function and facilitates myelin repair following demyelination. G protein-coupled receptors (GPCRs) represent a major target class in the druggable genome and are widely expressed in oligodendroglia. Targeting GPCRs involved in remyelination presents a tra…

Effect of Fingolimod on Neural Stem Cells: A Novel Mechanism and Broadened Application for Neural Repair.

Inflammatory demyelination and axonal damage of the CNS are hallmarks of multiple sclerosis (MS) and its animal model, experimental autoimmu … including ameliorated clinical signs and CNS inflammatory demyelination, enhanced MBP synthesis and remyelination, inhibited axonal degeneration, and reduced astrogliosis. Moreover, FTY720 significantly improved incorporation and survival of transplanted NSCs in the CNS and drove their differentiation into more OLGs but fewer astrocytes, thus promoting remyelin …

Transplantation of cryopreserved adult human Schwann cells enhances axonal conduction in demyelinated spinal cord.

Schwann cells derived from human sural nerve may provide a valuable source of tissue for a cell-based therapy in multiple sclerosis. However … hidium bromide lesioned dorsal columns of immunosuppressed Wistar rat. After 3-5 weeks of extensive remyelination, a typical Schwann cell pattern was observed in the lesion zone. Many cells in the lesion were immunopositive for an anti-human nuclei monoclonal antibody. The dorsal columns were removed and maintained in an in vitro recording chamber; the conducti …

Реакция олигодендроцитов на клетку олигодендроцитов на провокационное демиэлирование со старением.

Клетки потомства олигодендроцитов (OPC) способны к самовосстановлению, дифференцированию на зрелые миелинирующие клетки и восстановлению центральной нервной системы в ответ на обезвоживание. Нормальное старение связано с сокращением функциональных возможностей ОПС и вызывает различные транскрипционные подписи даже при отсутствии аутоиммунного провокационного демиэлирования. Чтобы определить, как старение влияет на реакцию ОРХ на острый подстрекательский оскорбление, сопоставимый с демиелинизирующим событием в множестве склероза (MS), мы провели приемную передачу молодых миелиново-реактивных ТТ

Совпадение в аннотации оригинала
Oligodendrocyte progenitor cells (OPCs) have the capacity to self-renew, differentiate into mature myelinating cells, and remyelinate the ce … uction of OPC differentiation in aged animals, there was no significant difference in the extent of remyelination observed for young and aged lesions. Aged OPCs rise to the challenge in response to a strong auto-immune attack, suggesting that compensatory strategies allow both young and aged OPCs to survive and remyelinate in the inflammatory environment. Ident …

Реакция олигодендроцитов на клетку олигодендроцитов на провокационное демиэлирование со старением.

Клетки потомства олигодендроцитов (OPC) способны к самовосстановлению, дифференцированию на зрелые миелинирующие клетки и восстановлению центральной нервной системы в ответ на обезвоживание. Нормальное старение связано с сокращением функциональных возможностей ОПС и вызывает различные транскрипционные подписи даже при отсутствии аутоиммунного провокационного демиэлирования. Чтобы определить, как старение влияет на реакцию ОРХ на острый подстрекательский оскорбление, сопоставимый с демиелинизирующим событием в множестве склероза (MS), мы провели приемную передачу молодых миелиново-реактивных ТТ

Совпадение в аннотации оригинала
Oligodendrocyte progenitor cells (OPCs) have the capacity to self-renew, differentiate into mature myelinating cells, and remyelinate the ce … uction of OPC differentiation in aged animals, there was no significant difference in the extent of remyelination observed for young and aged lesions. Aged OPCs rise to the challenge in response to a strong auto-immune attack, suggesting that compensatory strategies allow both young and aged OPCs to survive and remyelinate in the inflammatory environment. Ident …

Изучение роли нейропной защиты дериватива Sulfonamide KM11 в демиелинизации в модели Zebrafish с помощью модуляции антиоксидантов и воспаляющих цитокиновых путей.

Множественный склероз (MS) — гиперчувствительная реакция с повышенным воспалением, что приводит к обезвоживанию и нейронному дегенерации. В настоящее время для повышения способности к воспоминанию имеются ограниченные лекарственные средства. Цель этого исследования заключалась в оценке нейрозащитного и ремиелионирующего потенциала новой производной сульфонамида, KM11 [N-(7-гидрокси-1,3-бензотиазол-2-ил)-4-метилбензол-1-сульфонамид], в модели демиелинации у зебры. KM11 был синтезирован в лаборатории и опробован с использованием комплексного подхода. Клетки SH-SY5Y, обработанные KM11 (10-200 мкм

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a hypersensitivity reaction with increased inflammation, which leads to demyelination and neuronal degeneration. Currently, there are limited medications to improve the remyelination capacity. This study aimed to evaluate the neuroprotective and remyelinating potential of a novel sulfonamide derivative, KM11 [N-(7-hydroxy-1,3-benzo…

Гипоксичная нейроинфламмация в патогенезе множественного склероза.

Множественный склероз (MS) — аутоиммунная болезнь, которая повреждает миелиновую оболочку вокруг аксонов центральной нервной системы, что приводит к неврологической дисфункции. Хотя первоначальное повреждение вызвано воспалением, гипоксия была зарегистрирована в нескольких районах мозга пациентов MS, однако значение этого для прогнозирования и лечения остается неясным. Нейроинфламмация может вызывать гипоксию, а гипоксия может вызывать и усугублять нейроинфламму, образуя порочный круг. Повреждения MS часто сопровождаются обезвоживанием, которое может восстановить неврологическую функцию. Однак

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is an autoimmune disease that damages the myelin sheath around the central nervous system axons, leading to neurolog … e neuroinflammation, forming a vicious cycle. Within MS lesions, demyelination is often followed by remyelination, which may restore neurological function. However, demyelinated axons are vulnerable to damage, which leads to the accumulation of the permanent neurological dysfunction typical in MS, with this vulnerability heightened during hypoxia. Clinically ap …

Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination.

Despite current therapeutic strategies for immunomodulation and relief of symptoms in multiple sclerosis (MS), remyelination falls short due to dynamic neuropathologic deterioration and relapses, leading to accrual of disability and associated patient dissatisfaction. The potential of cannabinoids includes add-on immunosuppressive, analgesic, neuroprotective, and remyelinative effects. This study evaluates the efficacy of medical marijuana in MS and its experimental animal models. A systematic review was conducted by a literature search through PubMed, ProQuest, and EBSCO electronic databases …

Quantification and Localisation of New Brain Lipid Synthesis Using Deuterium Oxide and High Resolution Mass Spectrometry.

Myelin is the lipid-rich membrane that surrounds neuronal axons and is essential for neurological function in vertebrates. The development o … r of mice fed normal chow, chow containing the demyelinating toxin cuprizone, or during spontaneous remyelination following cuprizone withdrawal. Liquid chromatography-tandem mass spectrometry and mass spectrometry imaging were used to quantify and localise the newly synthesised, deuterated lipids. While most glycerophospholipids were constitutively deuterated, …

Focal white matter lesions induce long-lasting axonal degeneration, neuroinflammation and behavioral deficits.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) with episodes of inflammatory demyelination and remyelination. While remyelination has been linked with functional recovery in MS patients, there is evidence of ongoing tissue damage despite complete myelin repair. In this study, we investigated the long-term consequences of an acute demyelinating white matter CNS lesion. For this purpose, acute demyelination was induced by 5-week-cuprizone intoxication in male C57BL/6 J mice, and the tissues were examined after a 7-month recovery period. While myelin…

Преобразование фактора роста-β рецептора I киназы играет решающую роль в регенерации олигодендроцита после обезвоживания.

Множественный склероз (MS) — аутоиммунное заболевание, характеризующееся потерей олигодендроцитов (OL) и аксоновой демиелинацией в центральной нервной системе. Большинство терапевтических агентов сосредоточивают внимание на регулировании иммунной реакции путем подавления аутоиммунных реакций. Поэтому необходимо разрабатывать лечебные агенты, которые способствуют воспоминанию НО в тех местах, где заболевания уже подверглись обезвоживанию. В этом исследовании мы создали новую трансгенную зебру с высокой эффективностью для абляции OL и создали платформу на основе скрининга с высокой пропускной сп

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is an autoimmune disease characterized by the loss of oligodendrocytes (OLs) and axon demyelination in the central nervous system. Most therapeutic agents focus on regulating the immune response by suppressing autoimmune reactions. Therefore, developing therapeutic agents that promote remyelination by OLs at disease sites that have al…

Astrocyte-derived tissue Transglutaminase affects fibronectin deposition, but not aggregation, during cuprizone-induced demyelination.

Astrogliosis as seen in Multiple Sclerosis (MS) develops into astroglial scarring, which is beneficial because it seals off the site of central nervous system (CNS) damage. However, astroglial scarring also forms an obstacle that inhibits axon outgrowth and (re)myelination in brain lesions. This is possibly an important cause for incomplete remyelination in the CNS of early stage MS patients and for failure in remyelination when the disease progresses. In this study we address whether under demyelinating conditions in vivo, tissue Transglutaminase (TG2), a Ca2+ -dependent enzyme that catalyses…

Improving test-retest variability of visual-evoked responses in multiple sclerosis: implications for trial design.

Remyelination is an important repair strategy in multiple sclerosis. Latencies of visual-evoked responses are a suitable surrogate for remyelination of the optic nerve. Their test-retest variability has been incompletely evaluated, especially in pathologically delayed potentials. Visual-evoked potential was recorded twice, 2.1 +/- 3.1 (mean +/- SD) days apart, in 39 patients with definite or evaluated for multiple sclerosis. Acute optic neuritis and current steroid treatment were exclusion criteria. Mean and difference of the two recordings were calculated for latencies and amplitude, both bef…

Severe Guillain-Barré syndrome: sorting out the pathological hallmark in an electrophysiological axonal case.

We describe a clinicopathological study of a patient presenting with severe and electrophysiological axonal Guillain-Barré syndrome (GBS). A … anding lesions included dark fibers, scattered macrophage infiltration, and occasional images of de-remyelination or axonal degeneration. In the fifth spinal nerve, there was widespread loss of myelinated fibers with focal areas showing almost complete fiber loss and variable fascicular combination of extensive de-remyelination and axonal degeneration. Walleria …

Regenerating sciatic nerve does not utilize circulating cholesterol.

The rapid accumulation of myelin in the peripheral nervous system during the early postnatal period requires large amounts of cholesterol, a … cted 3H2O as precursor. The accumulation of additional cholesterol in nerve during regeneration and remyelination could all be accounted for by that locally synthesized within the nerve. There was also an increase in cholesterol esters in injured nerve segments; in crushed nerves, these levels decreased during regeneration and remyelination, consistent with reu …

Detecting early brain susceptibility changes before demyelination in cuprizone mouse model using quantitative susceptibility mapping (QSM).

Multiple sclerosis (MS) is a neurological disease that affects the central nervous system through demyelination and inflammation. Animal model, including the cuprizone (CPZ) model, provides a robust platform for studying demyelination and remyelination in MS. While conventional MRI techniques are sensitive to myelin changes, quantitative susceptibility mapping (QSM) offers additional advantages by capturing both myelin- and iron-related pathology. In this study, we performed longitudinal whole-brain multimodal magnetic resonance imaging (MRI), including T2-weighted imaging, magnetization trans…

Cytokine regulation by modulation of the NMDA receptor on astrocytes.

The N-methyl-d-aspartate receptor (NMDA-R) is crucial for synaptic transmission and plasticity. Over-activation, as well as complete blockade, of receptor function can lead to severe impairment. However, modest modulation of the receptor has been reported to be neuroprotective via endogenous regulation of the receptor and its subunit composition in response to pathophysiological conditions. As an important model for de- and remyelination in the central nervous system (CNS) we examined NMDA-R regulation in the mouse cuprizone model. We were able to show an upregulation of the NR2 subunit on hip…

Sphingosine-1-phosphate receptor antagonism enhances proliferation and migration of engrafted neural progenitor cells in a model of viral-induced demyelination.

The oral drug FTY720 affects sphingosine-1-phosphate (S1P) signaling on targeted cells that bear the S1P receptors S1P1, S1P3, S1P4, and S1P … preferential differentiation into oligodendroglia accompanied by axonal preservation, and increased remyelination. Cultured NPCs expressed transcripts for S1P receptors S1P1, S1P2, S1P3, S1P4, and S1P5. FTY720 treatment of cultured NPCs resulted in increased mitogen-activated protein kinase phosphorylation and migration after exposure to the chemokine CXCL12. A …

Oligodendrocyte progenitor cell susceptibility to injury in multiple sclerosis.

Remyelination in multiple sclerosis (MS) is often incomplete. In experimental models, oligodendrocyte progenitor cells (OPCs) rather than previously myelinating oligodendrocytes (OLs) are responsible for remyelination. This study compares the relative susceptibility of adult human OPCs and mature OLs to injury in actively demyelinating MS lesions and under in vitro stress conditions. In all lesions (n = 20), the number of OLs (Olig2 weak/NogoA positive) was reduced compared to control white matter (mean 38 ± 4% of control value). In 11 cases, OPC numbers (Olig2 strong; NogoA negative) were als…

Multiple Sclerosis and Other Acquired Demyelinating Diseases of the Central Nervous System.

Acquired demyelinating diseases of the central nervous system (CNS) comprise inflammatory conditions, including multiple sclerosis (MS) and related diseases, as well as noninflammatory conditions caused by toxic, metabolic, infectious, traumatic, and neurodegenerative insults. Here, we review the spectrum of diseases producing acquired CNS demyelination before focusing on the prototypical example of MS, exploring the pathologic mechanisms leading to myelin injury in relapsing and progressive MS and summarizing the mechanisms and modulators of remyelination. We highlight the complex interplay b…