固有免疫和适应性免疫分别参与急性和慢性脑缺血损伤，脑缺血抗炎治疗研究方兴未艾。半胱氨酸蛋白酶（Cathepsin S，Cat S)可以裂解神经细胞膜上的趋化因子Fractalkine（FKN），可能通过FKN加剧急性脑缺血的固有免疫反应；另外，Cat S是适应性免疫中的关键因子，可能参与缺血后的慢性自身免疫性脑损伤。我们的预实验发现，Cat S基因敲除可以保护小鼠局灶脑缺血后24 h神经功能或者组织学的损害，也可以保护局灶脑缺血后7 d之内的神经功能损害；Cat S抑制剂也可以保护急性脑缺血。由此，我们推测，Cat S可通过FKN途径参与急性缺血损伤；也可通过适应性免疫影响缺血后长期脑功能恢复。本研究中，我们将利用体、内外脑缺血模型（包括急性和长期模型）、采用基因敲除等手段，深入阐明Cat S在急性和长期脑缺血损伤中的作用和机制，探索Cat S抑制作为免疫调节在脑缺血治疗中的作用。

Immunity and inflammation are key elements of the pathobiology of stroke. Recent developments have revealed that stroke engages both innate and adaptive immunity.Anti-inflammatory and immunomodulation are promising therapeutic approaches. Cystein protease Cathepsin (Cat S) can liberate a kind of chemokine, fractalkine (FKN), from the membrane of neurons, and the free soluble FKN can aggravate inflammation during acute stroke by recruitment of inflammtory cells via chemotaxis. Cat S also plays a key role in antigen presentation and T cell adaptive immunity and could be engaged in chronic autoimmune brain damage after ischemia and influence long-term neurological recovery. Our preliminary experiments showed that Cat S gene knock out could protect against functional and tissue damage due to transient focal brain ischemia at 24 h after MCAO/reperfusion, and could protect against functional damage during 7 d after MCAO/reperfusion; Cat S inhibitor (LHVS, i.c.v) could also protect against acute brain ischemic damage at 24h. Therefore we hypothesizes that Cat S can aggravate acute brain ischemic damage via FKN pathway, and perniciously influence long-term neurological recovery via T cell adaptive immunity after stroke. In this study, we will use various research methods like gene knock-out to investigate the effects of Cat S on the acute and long-term brain ischemic damage in vivo and in vitro ischemic models (including acute and long term animal models), and try to carify the protective effect of Cat S inhibition,as a kinde of anti-inflammatory or immunomodulation agent,against brain ischemia.