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 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 mode of action of B-cells and therefore help to improve therapeutic options for progressive MS.
Highlights
Cortical demyelination represents a prominent feature of the multiple sclerosis (MS) brain, especially in progressive stages
Anti-CD20 treatment attenuates cortical demyelination Animals treated with an isotype control antibody before or after Myelin oligodendrocyte glycoprotein (MOG) immunization showed a statistically significant cortical demyelination, substantiated by the reduction of proteolipid protein (PLP)-immunoreactivity in both cerebral hemispheres, at 15 days after cytokine injection in comparison with the controls without cytokine injection (C1 ipsilateral: p < 0.02, C1 contralateral: p < 0.01, C2 ipsi: p < 0.03, C2 contra: p < 0.02) (Fig. 2a, b)
It is worth to note that the preserved PLP-immunoreactivity was slightly stronger in the group that was treated with anti-CD20 before the MOG immunization (E2), when compared to those treated afterwards (E1) but not reaching statistical significance
Summary
Cortical demyelination represents a prominent feature of the multiple sclerosis (MS) brain, especially in (late) progressive stages. RRMS is characterized by Haindl et al Journal of Neuroinflammation (2021) 18:138 inflammation and demyelination primarily driven by adaptive immunity, while in PMS, innate immune cells such as macrophages, dendritic cells, microglia, and natural killer cells play major roles, altogether emphasizing the multifaceted complexity in PMS pathogenesis This difference could partially explain the fact that immunomodulatory or immunosuppressive drug formulations that successfully improve RRMS have been fairly ineffective in the treatment of PMS [4, 5]. Clonally expanded plasma cells from MS patients produce antibodies directed against neurons and astrocytes but rarely against myelin components, suggesting that metabolic and energetic stress induced by inflammation could precede demyelination and impede remyelination These antibodies caused demyelination in spinal cord explants in vitro, indicating an antibody-mediated pathology [6, 7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
