Reaktive Astrozytenveränderungen in Multiple-Sklerose-Läsionen: Morphologische und immunhistochemische Analyse unter Berücksichtigung verschiedener Läsionsaktivitäten und immunpathologischer Subtypen

Abstract

Multiple sclerosis (MS) is a heterogeneous disease characterized by demyelination, inflammation, axonal loss, and astrogliosis. However, the role of astrocytes in the pathogenesis of MS lesions is not well understood. The present study aims at defining patterns of astroglial pathology in 124 MS biopsies. Additionally, 11 cases of progressive multifocal leukencephalopathy (PML) were investigated. Using immunocytochemistry against the glial acidic fibrillary protein (GFAP), the total number of reactive astrocytes and Creutzfeld-Peters cells, the number of astroglial cytoplasmic inclusions, and the density of cytoplasmic fibres were examined. Findings were stratified according to the immunopathological subtype. The highest numbers of reactive astrocytes as well as the highest densities of cytoplasmic fibres were identified in inactive remyelinated lesions. In contrast, cytoplasmic inclusions were associated with inactive demyelinated lesions without remyelination. In early active lesions significantly higher numbers of reactive astrocytes were detected in the autoimmune-mediated MS subtypes I and II (p<0.01 and p<0.001), while in pattern III, which is associated with oligodendrocyte pathology, the lowest numbers of reactive astrocytes were found. Furthermore, the number of reactive astrocytes in PML lesions, where virus-induced oligodendrocyte destruction takes place, was similar to pattern III lesions (p>0.05). Early active lesions revealed significantly higher numbers of Creutzfeld-Peters cells compared to inactive lesions, independent of the degree of de- or remyelination. Last but not least, reactive astroglial pathology was also identified in the periplaque white matter (PPWM), but to a lesser extent. Here, the highest numbers of reactive astrocytes were identified in the PPWM of pattern II lesions. The results of this study indicate a multifunctional role of astrocytes in the pathogenesis of MS. While in inactive lesions reactive astrogliosis may support the process of remyelination, distinct pattern s of reactive astrogliosis were identified in early active MS biopsies of different immunopathological subtypes. These findings strongly support the hypothesis of pathological heterogeneity in MS. However, further investigations are needed to elucidate the function of reactive astrogliosis within different immunosubtypes of MS.