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Неожиданное возрождение в отсутствие матричной металопротеины 7.

В множестве склерозов (MS) приток иммунных клеток в центральную нервную систему приводит к обезвоживанию мозга, зрительного нерва и спинного мозга. По мере того как MS прогрессирует, воспоминание становится все более неэффективным, что делает нейронные аксоны уязвимыми для дегенерации и приводит к постоянной неврологической инвалидности. При хронических поражениях MS аберрантная аккумуляция молекул внеклеточной матрицы (ECM), включая фибронектин и гиалуронан, ухудшает олигодендроцитную дифференциацию клеточных клеток, что ведет к сбоям в ремилинации. Таким образом, устранение ингибиторских УХМ

Совпадение в аннотации оригинала
In multiple sclerosis (MS), an influx of immune cells into the central nervous system leads to focal demyelinating lesions in the brain, optic nerve, and spinal cord. As MS progresses, remyelination increasingly fails, leaving neuronal axons vulnerable to degeneration and resulting in permanent neurological disability. In chronic MS lesions, the aberrant acc…

The Current Challenges for Drug Discovery in CNS Remyelination.

The myelin sheath wraps around axons, allowing saltatory currents to be transmitted along neurons. Several genetic, viral, or environmental factors can damage the central nervous system (CNS) myelin sheath during life. Unless the myelin sheath is repaired, these insults will lead to neurodegeneration. Remyelination occurs spontaneously upon myelin injury in healthy individuals but can fail in several demyelination pathologies or as a consequence of aging. Thus, pharmacological intervention that promotes CNS remyelination could have a major impact on patient's lives by delaying or even preventi…

Extensive remyelination of the CNS leads to functional recovery.

Remyelination of the CNS in multiple sclerosis is thought to be important to restore conduction and protect axons against degeneration. Yet the role that remyelination plays in clinical recovery of function remains unproven. Here, we show that cats fed an irradiated diet during gestation developed a severe neurologic disease resulting from extensive myelin vacuolation and subsequent demyelination. Despite the severe myelin degeneration, axons remained essentially intact. There was a prompt endogenous response by cells of the oligodendrocyte lineage to the demyelination, with remyelination occu…

Failure of remyelination in the nonhuman primate optic nerve.

The mechanisms limiting myelin repair in human central nervous system (CNS) remain unknown. Models of induced-demyelination in the nonhuman primate CNS may provide the necessary grounds to unravel these mechanisms and to investigate the development of strategies to promote myelin repair. To address this issue, we developed a model of focal demyelination in the adult Macaca fascicularis CNS. Lesions were induced by microinjection of lysolecithin in the optic nerve and the profile of remyelination was compared to that of lysolecithin-induced lesions of the spinal cord. In both structures, the ti…

Multicontrast MRI of remyelination in the central nervous system.

Although magnetic resonance imaging (MRI) represents the most sensitive tool for the detection of white matter abnormalities in patients with multiple sclerosis (MS), the heterogeneity of MS placques severely hampers the elucidation of specific pathophysiological processes. In order to identify putative MRI markers for de- and remyelination, we employed the cuprizone mouse model which leads to a selective and reversible demyelination of the corpus callosum with little or no axonal damage. Apart from histopathology, animals were studied with high-resolution three-dimensional MRI in vivo using m…

Biomaterial-Based Controlled Release Systems for Spinal Cord Remyelination.

Spinal cord injury (SCI) triggers a complex secondary injury cascade characterized by oligodendrocyte (OL) death and axonal demyelination, leading to permanent neurological deficits. Despite the presence of endogenous oligodendrocyte progenitor cells (OPCs), the inhibitory microenvironment-marked by inflammation, glial scarring, and biochemical barriers-prevents effective remyelination. Traditional pharmacological treatments are further hindered by the blood-spinal cord barrier and rapid clearance of intrathecal injections. This review examines the evolution of controlled release systems engin…

Microenvironmental Regulation of Central Nervous System Myelination and Remyelination.

Both myelination and remyelination in the central nervous system (CNS) rely on the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs). However, the microenvironment and underlying mechanisms of these two processes are significantly different. Myelination is driven by intrinsic developmental programs, whereas remyelination is triggered as a response to demyelinating injury. These distinct origins shape unique microenvironmental conditions that critically influence the respective processes. The microenvironment comprises, the extracellular matrix (ECM) a…

Сверхвековое воспоминание ассоциируется с дисрегулированными микроглиальными переходами.

Множественный склероз (MS) — хроническое, воспалительное состояние, характеризующееся нейродегенерацией и потерянным миелином, или обезвоживанием. Этот потерянный миелин может быть регенерирован у людей с MS в процессе, называемом воспоминание, который подвержен неудаче и страдает с возрастом. Ремиэлирование облегчается микроглией, но наше понимание микроглиальной реакции во время ремиелиции является неполным. Здесь мы описываем микроглиальную реакцию во время ремиелиции в мышиной модели лизолецитина с использованием последовательности одноклеточных RNA и находим несколько различных микроглиал

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic, inflammatory condition characterized by neurodegeneration and lost myelin, or demyelination. This lost myelin may be regenerated in people with MS through a process called remyelination, that is prone to failure and is impaired with age. Remyelination is facilitated by microglia but our understanding of the microglial re…

Gain of Olig2 function in oligodendrocyte progenitors promotes remyelination.

The basic helix-loop-helix transcription factor Olig2 is a key determinant for the specification of neural precursor cells into oligodendroc … ce. We found that Olig2 overexpression enhanced oligodendrocyte progenitor cell differentiation and remyelination. To assess the relevance of these findings in demyelinating diseases, we also examined OLIG2 expression in multiple sclerosis lesions. We demonstrate that OLIG2 displays a differential expression pattern in multiple sclerosis lesions that correlates …

Propentofylline reverses delayed remyelination in streptozotocin-induced diabetic rats.

OBJECTIVE: The diabetic state induced by streptozotocin injection is known to impair oligodendroglial remyelination in the rat brainstem following intracisternal injection with the gliotoxic agent ethidium bromide (EB). In such experimental model, propentofylline (PPF) recently showed to improve myelin repair, probably due to its neuroprotective, antiinflammatory and antioxidant effects. The aim of this study was to evaluate the effect of PPF administration in diabetic rats submitted to the EB-demyelinating model. MATERIALS AND METHODS: Adult male rats, diabetic or not, received a single inje…

Remyelination of optic nerve lesions: spatial and temporal factors.

Optic neuritis provides an in vivo model to study demyelination. The effects of myelin loss and recovery can be measured by the latency of t … inflammatory demyelination is probably the single most important factor determining completeness of remyelination. The time period favorable to remyelination is likely to be within the first 6 months after the attack.

Statin therapy inhibits remyelination in the central nervous system.

Remyelination of lesions in the central nervous system contributes to neural repair following clinical relapses in multiple sclerosis. Remyelination is initiated by recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. Simvastatin, a blood-brain barrier-permeable statin in multiple sclerosis clinical trials, has been shown to impact the in vitro processes that have been implicated in remyelination. Animals were fed a cuprizone-supplemented diet for 6 weeks to induce localized demyelination in the corpus callosum; subsequent return to norm…

Targeting of IgMkappa antibodies to oligodendrocytes promotes CNS remyelination.

We previously identified the remyelinating activity of a natural IgMkappa oligodendrocyte-reactive autoantibody (SCH94.03), using a virus-induced murine model of multiple sclerosis. We now describe a second mouse IgMkappa monoclonal antibody (mAb) (SCH79.08) raised against normal mouse spinal cord homogenate, which reacts with myelin basic protein and also promotes remyelination. Because these two mAbs recognize different oligodendrocyte antigens, several previously identified oligodendrocyte-reactive IgMkappa mAbs (O1, O4, A2B5, and HNK-1), each with distinct antigen specificities, were evalu…

Дигидроартемизинин усиливает ремиелионацию, переключая микроглию на репаративный фенотип.

По общему признанию, одним из наиболее мощных подходов к демиелинизационной терапии является бурный ремонт миелина, что в основном способствует восстановлению неврологических функций. Поддержание иммунной гомеостази в микроглии является предпосылкой для создания репаративной среды для миелина. Дигидроартемизин (ДХА) клинически эффективен в изменении иммунологического статуса и предполагает возможность лечения демиелинизирующих заболеваний. Однако его значение для прореалионации остается неясным.МЕТОДЫ: Сначала мы провели оценку воздействия ДГВ на нейрофункциональное восстановление и целостност

Совпадение в аннотации оригинала
BACKGROUND: Boosting myelin repair is widely recognized as one of the most powerful approaches for demyelinating therapy, essentially contri … gical status and implies potential in treating demyelinating disease. However, its relevance to pro-remyelination remains unclear. METHODS: We first evaluated the effects of DHA on neurofunctional recovery and white matter integrity in chronic experimental autoimmune encephalomyelitis (EAE), an ideal model for secondary progressive multiple sclerosis (SPMS) ch …

Motor Learning and Physical Exercise in Adaptive Myelination and Remyelination.

The idea that myelination is driven by both intrinsic and extrinsic cues has gained much traction in recent years. Studies have demonstrated … structured and repetitive bodily movements that expend energy and benefits one's fitness, promotes remyelination in pathology, but it is less clear whether it promotes adaptive myelination in healthy subjects. Studies on these topics have also investigated whether the timing of motor learning or physical exercise is important for successful addition of myelin. …

Clobetasol promotes remyelination in a mouse model of neuromyelitis optica.

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system that can produce marked neurological defic … inimal axonal damage. The FDA-approved drug clobetasol promoted differentiation in OPC cultures and remyelination in cerebellar slice cultures and in mice. Intraperitoneal administration of 2 mg/kg/day clobetasol reduced myelin loss by ~60 %, even when clobetasol was administered after demyelination occurred. Clobetasol increased the number of mature oligodendr …

Strategies for protecting oligodendrocytes and enhancing remyelination in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) characterized by encephalitogeni … s of demyelination, the spontaneous ability of the CNS to regenerate, and the inevitable failure of remyelination. From this a number of promising molecular targets have been identified to protect oligodendrocytes and promote remyelination. Combining immunomodulatory therapy with strategies to protect oligodendrocytes from further degeneration and enhance remye …

Oligodendrocyte PTEN is required for myelin and axonal integrity, not remyelination.

OBJECTIVE: Repair of myelin injury in multiple sclerosis may fail, resulting in chronic demyelination, axonal loss, and disease progression. As cellular pathways regulated by phosphatase and tensin homologue deleted on chromosome 10 (PTEN; eg, phosphatidylinositol-3-kinase [PI-3K]) have been reported to enhance axon regeneration and oligodendrocyte maturation, we investigated potentially beneficial effects of Pten loss of function in the oligodendrocyte lineage on remyelination. METHODS: We characterized oligodendrocyte numbers and myelin sheath thickness in mice with conditional inactivation…