Anti-CD20 Treatment Effectively Attenuates Cortical Pathology in a Rat Model of Widespread Cortical Demyelination

Abstract

BackgroundCortical demyelination represents a prominent feature of the multiple sclerosis (MS) brain, especially in (late) progressive stages. We recently developed a new rat model that reassembles critical features of cortical pathology characteristic to progressive types of MS. In persons affected by MS, B-cell depleting anti-CD20 therapy proved successful in the relapsing remitting as well as the early progressive course of MS, with respect to reducing the relapse rate and number of newly formed lesions. However, if the development of cortical pathology can be prevented or at least slowed down is still not clear. The main goal of this study was thus to increase our understanding for the mode of action (MOD) of B-cells and B-cell directed therapy on cortical lesions in our rat model. MethodsFor this purpose, we set up two separate experiments, with two different induction modes of B-cell depletion. Brain tissues were analyzed thoroughly using histology. ResultsWe observed a marked reduction of cortical demyelination, microglial activation, astrocytic reaction and apoptotic cell loss in anti-CD20 antibody treated groups. At the same time, we noted increased neuronal preservation compared to control groups, indicating a favorable impact of anti-CD20 therapy. ConclusionThese findings might pave the way for further research on the MOD of B-cells and therefore help to improve therapeutic options for progressive MS.