Inhibition of the Platelet-Receptor P2Y12 Moderates Neuroinflammation

Patients suffering from multiple sclerosis (MS) have an augmented risk for cardiovascular diseases associated with abnormal platelet functions. However, platelet-mediated contributions to inflammatory disorders of the central nervous system (CNS), such asexperimental autoimmune encephalomyelitis (EAE), a model to study MS, remain poorly understood.In EAE, platelets were found accumulating in the CNS parenchyma, thereby amplifying the (neuro) inflammatory response. Materials and Methods: Here, we show that pharmacologic blockade of platelet-receptor P2Y12 with elinogrel renders mice less susceptible to EAE. Results: While disease onset was unaltered, elinogrel treatment was associated with a reduced (p<0.03) disease maximum and also with reduced prevalence of inflammatory infiltrates compared to the control group (5,1 ± 1,4% versus 9,6 ± 1,2%, n=6, p<0.05). Amelioration was ccompanied by reduced numbers of interleukin-17A-producing T-helper cells as determined via intracellular cytokine staining atthe disease peak (day 15). Further, an increase in CD8+ and CD8+CD11c+ cells, but no significant difference in macrophages, microglia, B-cells and plasmatic dendritic cells of elinogrel-treated mice was found. Conclusion: Overall, our findings show that inhibition of platelet activation is beneficial in an animal model of MS and thus indicate in addition to the classical immunological-orien ted pathophysiological concepts analternative strategy for the treatment of MS.