Brain, Vol. 117, No. 6, 1311-1322, 1994
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Patterns of oligodendroglia pathology in multiple sclerosis
ck41Research Unit for Experimental Neuropathology, Austrian Academy of Sciences Vienna, Austria 2Institute of Neurology, University of Vienna Vienna, Austria 3Department of Neurology, Hospital Lainz and L. Boltzmann Institute of Clinical Neurobiology Vienna, Austria 4Department of Neuropathology, University of Gottingen Germany 5Utano National Hospital Kyoto, Japan
Correspondence to:
Correspondence to: Professor Dr Hans Lassmann, Research Unit for Experimental Neuropathology, Austrian Academy of Sciences, Schwarzspanierstrasse 17, A-1090 Wien, Austria
Patterns of inflammation, demyelination and oligodendrocyte pathology were studied in acute multiple sclerosis and during early and late exacerbations of chronic multiple sclerosis. Cells within lesions were identified by immunocytochemistry with markers for T lymphocytes, macrophages, oligodendro-cytes and astrocytes. In addition, in situ hybridization for proteolipid protein mRNA was used to identify myelinating and myelin supporting oligodendrocytes. Degenerating cells in the lesions were detected by DNA fragmentation in cell nuclei. The inflammatory reaction in all three types of multiple sclerosis lesions was shown to be dominated by T lymphocytes and macrophages. In late chronic multiple sclerosis lesions, a significant increase in the number of immunoglobulin producing plasma cells was found in infiltrates as compared with acute and early multiple sclerosis lesions. In all three types of multiple sclerosis, confluent plaques of demyelination were found to be present. In acute multiple sclerosis, demyelination was found to be associated with extensive destruction of other tissue elements, including oligodendrocytes, astro-Acytes and axons, but even in these destructive lesions a considerable number of oligodendrocytes was preserved and at disposal therefore, for rapid remyelination. During early exacerbations of chronic multiple sclerosis, selective demyelination was associated with almost complete preservation of oligodendrocytes in the majority of cases. Correspondingly, a high number of remyelinating lesions was present at that stage of disease. In lesions developing late after onset of multiple sclerosis, demyelination generally accompanied extensive destruction and loss of oligodendrocytes. In these lesions, remyelination was sparse and restricted to lesional borders. The observed patterns of cell death suggest that in some cases oligodendrocytes, in others myelin sheaths are the primary target of the destructive process. Our data indicate that the type and amount of inflammation, de- and remyelination, and of tissue damage vary between different forms of multiple sclerosis and between different stages of the disease, possibly reflecting different pathogenic mechanisms in a disease spectrum.
multiple sclerosis; oligodendrocytes; demyelination; remyelination; myelin
Received April 8, 1994. Revised July 10, 1994. Accepted July 19, 1994.
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