Medical_University_Graz
Department_of_Neurosurgery

Author Of 1 Presentation

Experimental Models Poster Presentation

P0940 - Anti-CD20 therapy prevents cortical demyelination in a new rat model (ID 342)

Speakers
Presentation Number
P0940
Presentation Topic
Experimental Models

Abstract

Background

Cortical demyelination is thought to be a substrate for diffuse cognitive impairment often seen in the progressive stage of multiple sclerosis (MS). Unlike white matter plaques in brain or spinal cord, cortical MS lesions lack inflammatory T-cell infiltrates. B-cell depleting anti-CD20 therapy is effective in the relapsing-remitting course of MS, however not much is known about a possible effect of anti-CD20 directed therapy in prevention of cortical grey matter demyelination.

Objectives

We recently developed a new rat model (Ücal et al., 2017), suitable for research of cortical demyelination and associated cellular hallmarks seen in progressive MS. The aim of our study was to investigate the effect of anti-CD20 therapy on the development of cortical grey matter pathology in this model.

Methods

Adult male Dark Agouti rats were implanted with a catheter into the cerebral cortex, immunized with a low dose of a recombinant myelin oligodendrocyte glycoprotein (MOG) in incomplete Freund’s Adjuvant and injected with pro-inflammatory cytokines through the catheter to induce cortical demyelination. Anti-CD20 antibody therapy was administered either after (Group 1) or before (Group 2) MOG immunization by intravenous injection into the tail base vein. Rats were sacrificed at peak disease (day 15 post-cytokine injection). Cortical demyelination, microglial activation, neuronal cell loss, astrocytic reactivity and apoptotic cells were assessed by immunohistochemistry using specific markers (PLP, Iba1, NeuN, GFAP, Caspase3, respectively).

Results

Histological analysis demonstrates a significant reduction of demyelination, microglial activation, neuronal loss, astrocyte activation as well as apoptotic cells in anti-CD20 treated animals, compared to animals treated with an isotype-matched control antibody. Both therapeutic approaches (Group 1 and Group 2) showed equal efficacy. There was no significant difference in cortical demyelination between the healthy control animals (0.0 PLP loss) and the anti-CD20 treated animals (Group 1 = 0.1 PLP loss/mm2; Q1 = 0.03, Q3 = 0.27; Group 2 = 0.1 PLP loss/mm2; Q1 = 0.02, Q3 = 0.07).

Conclusions

Anti-CD20 therapy preserves the investigated cortical structures in our animal model, indicating a role of B-cells in the formation of cortical pathology, presumably through various pathways. These findings pave the way for further research on the mode of action of B-cells and might improve our understanding of cellular mechanisms behind progressive MS. This may expand our therapeutic strategies for MS patients in the progressive disease stage.

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