Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Dohrmann, J.
Effect of anti-CD20 therapy on cortical demyelination in a new rat model
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2021. pp. 69
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Haindl Michaela Tanja
- Hochmeister Sonja
- Altmetrics:
- Abstract:
- Background Cortical demyelination is a remarkable feature of multiple sclerosis (MS), especially in the late progredient phase, and is believed to be a substrate for the diffuse cognitive disorder. In clinical trials, B-cell depleting anti-CD20 antibody therapy has proven to be effective in the relapse-remitting as well as the early progressive stage of MS. However, if this therapy can prevent the development of cortical pathology is yet unknown. Objectives We recently created a new rat model (Üçal et al, 2017) that is adequate for research on cortical demyelination and affiliated cellular signs in progressive MS. The aim of this study was to explore the impact of anti-CD20 therapy on the formation of cortical lesions in our new rat model and thus to increase the knowledge for the modus operandi of B-cells. Methods Rats were implanted with a catheter into the cerebral cortex, immunized with myelin oligodendrocyte glycoprotein (MOG) and injected with pro-inflammatory cytokines to stimulate cortical demyelination. We set up two experimental groups in which anti-CD20 therapy was applied either after or before MOG immunization. Animals were sacrificed at peak disease and brain matter was histologically analyzed. Results Histological analysis of the different cellular markers discovered that anti-CD20 therapy averted cortical pathology showing significant diminution in demyelination, microglial activation, apoptotic cells, astrocytic reactivity and neuronal loss in anti-CD20 treated animals in contrast to animals given an isotype-matched control antibody. Both experimental groups showed equal efficacy. While there is a significant difference between the healthy control (HC) and the control antibody groups, the difference between the HC and the anti-CD20 antibody groups did not reach significance indicating similarity of the anti-CD20 treated animals to the healthy animals. Conclusions Our findings suggest a favorable impact of anti-CD20 therapy on conservation of the investigated structures indicating a contribution of B-cells in the development of cortical pathology, probably through various pathways. These promising results provide the basis for further research on the mechanism of tissue damage in the late phase of MS and might help to expand therapeutic schemes for progressive MS patients or even prevent progression in the first place.