The formation of a glial scar does not prohibit remyelination in an animal model of multiple sclerosis

In the demyelinating scenario of MOG EAE in the DA rat the astroglial reaction does not impede plaque repair. A finely regulated expression of astrocytic factors is necessary to promote OPC guidance, migration, differentiation, and survival. AbstractThe role of astrocytes in the pathophysiology of multiple sclerosis (MS) is discussed controversially. Especially the formation of the glial scar is often believed to act as a barrier for remyelination. At the same time, astrocytes are known to produce factors that influence oligodendrocyte precursor cell (OPC) survival. To explore these mechanisms, we investigated the astrocytic reaction in an animal model induced by immunization with myelin oligodendrocyte glycoprotein (MOG) in Dark Agouti (DA) rats, which mimics most of the histological features of MS. We correlated the astroglial reaction by immunohistochemistry (IHC) for glial fibrillary acidic protein (GFAP) to the remyelination capacity by in situ hybridization for mRNA of proteolipid protein (PLP), indicative of OPCs, over the full course of the disease. PLP mRNA peaked in early remyelinating lesions while the amount of GFAP positive astrocytes was highest in remyelinated lesions. In shadow plaques, we found at the same time all features of a glial scar and numbers of OPCs and mature oligodendrocytes, which were nearly equal to that in unaffected white matter areas. To assess the plaque environment, we furthermore quantitatively analyzed factors expressed by astrocytes pre...
Source: Glia - Category: Neurology Authors: Tags: RESEARCH ARTICLE Source Type: research