目前，缺血性脑卒中除早期溶栓外依然缺乏切实有效的治疗方法。因此，探索脑卒中的神经损伤及保护的新机制和新靶标、研发促进卒中后恢复的治疗策略迫在眉睫。1-磷酸鞘氨醇（sphingosine 1-phosphate，S1P）由鞘氨醇激酶（sphingosine kinases，SPKs）磷酸化鞘氨醇而产生。S1P通过激活其相应的的受体而调节多种生命活动过程。已有研究提示SPKs/S1P信号通路可能是脑卒中干预的潜在靶标，但其中的具体机制尚不清楚。本申请项目在发现S1P信号通路可调节脑卒中进程及卒中后神经炎症的工作基础上，拟进一步研究、阐明SPK2对缺血性脑卒中后小胶质细胞活化和M1-M2极化的调节作用及机制；揭示SPK2对小胶质细胞介导的神经炎性动态反应的重要调节作用。预期研究结果将为脑卒中病理机制的研究和基于SPK2的卒中治疗新药的研发提供新靶标和实验依据，为脑卒中的临床治疗提供新的有益思路。

There is still a lack of effective drugs or methods for ischemic stroke in the clinical treatment, in addition to early treatment with thrombolysis. Therefore, it is urgent to explore the new mechanisms and find new targets for neuroprotection, and to develop the new therapeutic strategies for stroke. Sphingosine 1-phosphate(S1P) is produced from sphingosine phosphorylated by sphingosine kinase 1 or 2 (SPK1, SPK2). S1P can regulate many biological processes via activating sphingosine 1-phosphate receptor 1-5 (S1PR1-5). Increasing evidence has revealed that SPKs/S1P signaling pathway may be a potential target for stroke. However, the involved mechanisms of SPKs/S1P regulating the pathological process of stroke remains unclear. Based our previous findings that S1P and its signaling pathways could regulate the process of ischemic stroke and inhibit neuroinflammation, the application is to demonstrate the impacts of SPK2 on activation and M1-M2 polarization of microglia after ischemic stroke, and to reveal the important roles of SPK2 in dynamic response of microglia-mediated neuroinflammation in stroke. The prospective results will provide a new and helpful strategy for prevention and treatment of stroke, and provide evidence for revealing new pathological mechanisms of stroke, and for developing new drugs targeting on SPK2 in the future.