外周和中枢继发炎性反应是脑卒中高致残和高死亡率的重要原因，但缺乏有效治疗措施。本课题组利用脑中动脉闭塞(MCAO)小鼠和氧-糖剥夺(OGD)细胞缺血模型发现，星型胶质细胞源性IL-17A可通过Caspase-12依赖的内质网应激细胞凋亡途径加重神经元缺血损伤。本课题拟通过特异沉默星形胶质细胞内IL-17A表达和IL-17A单克隆中和抗体，明确IL-17A对缺血性脑卒中后血脑屏障、炎症反应以及氧化应激的影响；借助神经生物学、生物化学和分子生物学等技术，探明缺血性卒中后血脑屏障破坏程度的时效性，筛选外周给予IL-17A单克隆中和抗体的最佳时间窗；阐明IL-17A通过影响PLC特定亚型，激活Calpain1/2以及提高GRP78和CHOP表达，从而加重Caspase-12依赖的细胞凋亡机制。所获成果将丰富人们对IL-17A在缺血性卒中机制的认识，为临床靶向IL-17A治疗缺血性卒中提供依据。

For ischemic stroke, the secondary inflammatory reaction in peripheral and central system is one of the major causes of high disability and mortality, but it’s still lacking effective treatment at present. Using the models of middle cerebral artery occlusion (MCAO)-induced ischemic stroked mice in vivo and oxygen-glucose deprivation (OGD)-mimicked cell ischemia in vitro, we have found that the astrocyte-derived IL-17A could aggravate the neuronal ischemic injuries via Caspase-12-dependent endoplasmic reticulum stress apoptotic pathway. Accordingly, the methods of specific silencing of IL-17A expression in astrocytes and IL-17A monoclonal neutralizing antibody exogenous administration were applied to clarify the role and mechanism of IL-17A in the blood-brain barrier damage, peripheral and central inflammatory responses, and brain oxidative stress after ischemic stroke; the techniques such as neurobiology, biochemistry and molecular biology were used to determine the timeliness of the blood-brain barrier damage after ischemic stroke, and to identify the optimal time window for peripheral administration of IL-17A monoclonal neutralizing antibody; in addition, the detailed molecular mechanism underlying IL-17A augmentation of neuronal apoptosis will be elucidated through Caspase-12-dependent endoplasmic reticulum stress to affect the activation of PLC specific subtype and Calpain1/2, and then increase the expression of GRP78 and CHOP. These achievements will enrich our understanding of the role and mechanism of IL-17A in the pathogenesis of ischemic stroke, and provide experimental evidence for clinical targeting of IL-17A in the treatment of ischemic stroke.