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Myelin Repair (myelin + repair)
Selected AbstractsRegulation of SVZ-derived gliogenesis by inflammatory-demyelinationJOURNAL OF NEUROCHEMISTRY, Issue 2002A. Baron-Van Evercooren Identifying a source of cells with the capacity to generate oligodendrocytes in the adult CNS would help the development of strategies to promote myelin repair. During development of the neonate rodent forebrain, most oligodendrocytes derive from the subventricular zone (SVZ), a germinative area which also contributes to the genesis of astrocytes and neurons. While the SVZ persists in the adult brain, its size is largely reduced and its contribution to cell genesis is essentially restricted to the renewal of the granular and periglomerular neurons of the olfactory bulb. Lesion derived signals can have a profound impact on the behavior of the SVZ cells. While cortical trauma triggers their mobilization and differentiation in astrocytes in the lesioned cortex (Holmin et al. 1997), focaly-induced demyelination promotes their migration in the demyelinated white matter and differentiation in astrocytes and oligodendrocytes (Nait-Oumesmar et al. 1999). Using EAE, we will show that multifocal demyelination (i) promotes the proliferation of the SVZ precursors (ii) enhances their migration towards the olfactory bulb and triggers their mobilization to multiple sites of the diseased white matter, and (iii) induces their differentiation in neurons, astrocytes and oligodendrocytes in the olfactory bulb, and in oligodendrocytes and astrocytes in the demyelinated white matter. SVZ precursors could thus be a source of oligodendrocytes and contribute with oligodendrocyte progenitors to the replacement of lost oligodendrocytes in demyelinating diseases of the adult CNS. [source] Bone morphogenetic proteins 4, 6, and 7 are up-regulated in mouse spinal cord during experimental autoimmune encephalomyelitisJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2008Jahan Ara Abstract Although spontaneous remyelination occurs in multiple sclerosis (MS), the extent of myelin repair is often inadequate to restore normal function. Oligodendrocyte precursors remaining in nonremyelinating MS plaques may be restricted by an inhibitory signal. Bone morphogenetic proteins (BMPs) have been implicated as repressors of oligodendrocyte development and inducers of astrogliogenesis. We hypothesized that BMPs are up-regulated in MS lesions and play a role in demyelination and astrogliosis. We examined expression of BMPs in an animal model of MS, chronic experimental autoimmune encephalomyelitis (EAE) induced by the myelin oligodendrocyte glycoprotein (MOG) peptide in C57BL/6 mice. By 14 days postimmunization, compared to those of control mice, the lumbar spinal cords of MOG-peptide EAE mice demonstrated prominent astrogliosis, infiltration of inflammatory cells, and disrupted expression of myelin proteins. Quantitative RT-PCR showed that expression of BMP4, BMP6, and BMP7 mRNA increased 2- to 4-fold in the lumbar spinal cords of animals with symptomatic EAE versus in vehicle-treated and untreated controls on days 14, 21, and 42 postimmunization. BMP2 mRNA expression was not altered. BMP4 mRNA was much more abundant in the spinal cords of all animals than was mRNA encoding BMP2, BMP6, and BMP7. Immunoblot analysis confirmed the increased expression of BMP4 in the EAE animals. Immunohistochemistry revealed increased BMP4 immunoreactivity in areas of inflammation in MOG-peptide EAE animals. BMP4 labeling was mostly limited to macrophages but was sometimes associated with astrocytes and oligodendrocytes. These results indicate that members of the BMP family are differentially expressed in adult spinal cord and are up-regulated during EAE. © 2007 Wiley-Liss, Inc. [source] Promotion of central nervous system remyelination by induced differentiation of oligodendrocyte precursor cells,ANNALS OF NEUROLOGY, Issue 3 2009Sha Mi PhD Objective Repair of demyelinated axons in diseases such as multiple sclerosis requires activation of the myelination program in existing or newly recruited oligodendrocyte precursor cells (OPCs). The control of OPC differentiation and initiation of myelination during repair is poorly understood. In this study, we test the ability of anti,LINGO-1 reagents to promote myelination in vitro and remyelination in the rodent adult central nervous system in vivo. Methods The effects of LINGO-1 antagonists on the differentiation of OPCs and the promotion of myelination has been assayed using a combination of coculture and slice culture preparations. Using three different animal models of demyelination and remyelination, we morphologically and functionally assessed the effects of LINGO-1 antagonists on OPC differentiation and myelin repair. Results The data indicate that in vitro treatment with antagonists of LINGO-1 promote OPC differentiation and myelination, whereas in vivo remyelination is accelerated in lysophosphatidylcholine- or cuprizone-induced demyelination. This remyelination is associated with enhanced OPC differentiation and functional recovery of conduction velocities in demyelinated axons. Interpretation Our studies demonstrate that LINGO-1 antagonism promotes OPC differentiation and remyelination, and suggest LINGO-1 functions as an inhibitor of OPC differentiation to retard central nervous system remyelination. Ann Neurol 2009;65:304,315 [source] The basis for treatment in multiple sclerosisACTA NEUROLOGICA SCANDINAVICA, Issue 2006A. Compston Contemporary licensed treatments for multiple sclerosis fail to provide a solution for the disease because their effects are limited to a modest reduction in the frequency of new episodes. They do not reduce disability or materially influence the progressive phase of the disease. A contemporary strategy for management requires a more detailed analysis of the separate contributions to the clinical features and overall course made by inflammation, axonal injury, compensatory mechanisms, and remyelination. From this formulation emerges the need either for early and fully effective suppression of the inflammatory response, limiting the damage to all components of the axon-glial unit; or the development of strategies for axonal and myelin repair that solve the issues of controlled differentiation, delivery and timing of these cell and growth factor-based interventions. [source] | |||||||||||||