Quantitative Untersuchung der Oligodendrozytendichte im Kortex von Callithrix-jacchus Marmosetten mit Experimenteller Autoimmuner Enzephalomyelitis

Quantitative Untersuchung der Oligodendrozytendichte im Kortex von Callithrix-jacchus Marmosetten mit Experimenteller Autoimmuner Enzephalomyelitis

Quantitative analysis of oligodendroglial densitiy in the cortex of callithrix-jacchus marmosets with experimental autoimmune encephalomyelitis

Andrea Christina Vondran

Dissertation

Datum der mündl. Prüfung: 2013-11-26

Erschienen: 2013-11-01

Betreuer: Brück, Wolfgang Prof. Dr.

Gutachter: Brück, Wolfgang Prof. Dr.

Gutachter: Flügel, Alexander Prof. Dr.

Gutachter: Oppermann, Martin Prof. Dr.

Zum Verlinken/Zitieren: http://hdl.handle.net/11858/00-1735-0000-0001-BC1C-E

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Zusammenfassung

Englisch

Histopathological studies of Multiple sclerosis (MS) are usually limited by the fact that autopsy tissue is usually from patients in the chronic stage of the disease. Thus far there are only few results on the pathology of oligodendrocytes in early cortical lesions in patients with MS. The recent findings on the pathogenesis of MS in the early stages of the disease are essentially based on the animal model of experimental autoimmune-mediated encephalomyleitis (EAE). The distribution pattern of EAE in the marmoset monkey is similar to the MS. In both diseases cortical lesions can be detected. The aim of this study was to investigate the pathology of oligodendrocytes in early cortical lesions in the EAE animal model. The densitiy of p25- and NogoA-positive oligodendrocytes was determined in the deep cortical layers in demyelinated and normal-appearing cortex. Furthermore, the density of macrophages, CD3-positive T-cells, CD20-positive B-cells and IgG-positive plasmacells in lesions was determined. The density of oligodendrocytes was significantly reduced in lesions compared with normal appearing cortex, resulting with a significantly higher proportion of p25-positive oligodendrocytes within the lesions compared to NogoA-positive oligodendrocytes. Quantitative analysis of inflammatory cells in the lesions revealed a majority of macrophages followed by T-cells, B-cells and few plasmacells. The results of this work show that oligodendrocyte loss is already common in demyelinated cortical lesions in marmosets with early stage of EAE. Since EAE in the marmosets is the animal model with the highest similarity to the human MS, these results suggest that also in early cortical MS lesions oligodendrocytes occur damage by a T-cell mediated antibody/complement reaction.

Keywords: Multiple sclerosis; oligodendrocytes; cortical lesions; Experimental autoimmune-mediated encephalomyelitis