促红细胞生成素（Erythropoietin, EPO）对脑缺血保护作用仍然是目前研究热点。本项目组一直致力于研究如何避免EPO副作用，最大限度行使EPO神经保护作用。前两个国自然面上项目分别从穿透血管脑屏障及大脑中动脉直接给药两个方面进行了相关研究。其他学者以及我们的研究结果发现仍然存在的问题：①动物多数集中在急性期研究，临床终点多是恢复期甚至康复期。②动物实验多是青壮年动物，且多数在缺血早期用药，与临床差异较大。③我们前期跨血脑屏障融合蛋白以及大脑中血管直接给药和其他学者EPO衍生物及给药方式的研究均存在局限性。EPO相对安全性（早已应用于贫血治疗）及现今缺乏有效神经保护药物使我们继续进行EPO的保护作用研究。本项目应用老龄小鼠研究延迟应用一种新的去除红细胞生成作用的变构EPO(mEPO)对脑缺血再灌注不同时期（尤其康复期）的血管神经新生修复作用及机制，为mEPO临床转化提供可靠依据。

The research on protective effect of ischemic by erythropoietin(EPO) is still a research hotspot. We have devoted ourselves to studying how to avoid the side effects of EPO and get the most neuroprotective effects out of it for a long time. Our two grants of National Science Foundation of China is about the neuroprotection of EPO.One is about EPO-TAT which can penetrate the blood brain barrier. The other one is about the administration of EPO via middle cerebral artery. However, there still remains several problems to be solved in our current studies as well as that of other researchers: ① Most animal experiments are performed during acute stage, but clinical endpoint is more closely correlated with convalescence and rehabilitation period. ② Most experimental animals are young or adult, and generally administrated in the early phase of ischemia, which is extremely different from clinical patients. ③ There is boundedness in our previous studies and relevant studies by other researchers. As a result, it is necessary to continue the researches on the neuroprotective effects of EPO, for lack of efficacious neuroprotective drugs and relative safety of EPO (which has already been applied to anemia therapy in clinical practices for a long time).Therefore, we will explore the impact and mechanism of effects of delayed administration of mutant EPO, which has been newly developed with enhanced neuroprotective effects and without erythropoietic activity,on angiogenesis and neurogenesis in different stages after aged mice cerebral ischemia-reperfusion (especially in convalescence and rehabilitation period).This research will provide a reliable basis for clinical trials of mutant EPO.