IL-17A promotes myelin loss and inflammatory response during Cuprizone-induced demyelination

resident microglia (MG) and peripheral immune cells infiltrating into the region surrounding the infarct core and leading to secondary neurodegeneration. Current clinical therapies using thrombolytic and anti-platelet agents are limited by temporal restrictions and do not prevent the secondary, inflammation-related CNS damage. Therefore, the development of new anti-inflammatory therapies in ischemic stroke is necessary and urgent. Interferon beta (IFNbeta), a cytokine with immunomodulatory properties, was approved by the FDA for the treatment of relapsing–remitting multiple sclerosis for more than a decade. Its anti-inflammatory properties and well characterized safety profile suggest that IFNbeta has therapeutic potential for the treatment of ischemic stroke. We evaluated the therapeutic effect of IFNbeta treatment in the ischemic stroke animal model, murine transient middle cerebral artery occlusion/reperfusion (MCAO/R), as well as the regulatory effect of IFNbeta treatment on the infiltration of inflammatory peripheral immune cells into CNS infarcted region. Our results showed that IFNbeta treatment dramatically decreased infarct size in ischemic brains and that is correlated with significantly reduced neurological scores. In addition, the infiltration of inflammatory peripheral immune cells, including neutrophils and dendritic cells/macrophages, was also largely decreased in ischemic brains of IFNbeta-treated stroke mice, compared to those of control stroke mice. As MG activation and subsequent release of inflammatory cytokines in the ischemic brains exacerbate the disease of stroke, we compare MG activation and inflammatory cytokine expression in the ischemic brains of IFNbeta-treated and control stroke mice. We observed that IFNbeta treatment not only suppressed MG activation, but also inhibited inflammatory cytokine IL-1beta and MMP-9 expression in the ischemic brains. Taken altogether, our results demonstrate that IFNbeta confers a protective effect against ischemic stroke through its anti-inflammatory properties. (The study is supported by AHA grant 12SDG8170005 to JY.)