中文摘要
申请人在缺血性脑卒中损伤后的神经血管新生机制方面作出了原创性研究。明确了趋化因子CXCL12 (SDF1)在卒中发病后不同时期的功能差异性,并针对此特性进行了小分子干预和基因治疗。近三年在Stroke等期刊上发表SCI论文32篇,累计影响因子超过140。作为第二完成人获2013年教育部自然科学二等奖。.项目专注缺血性卒中的恢复期,拟进一步研究CXCL12基因修饰的内皮祖细胞(EPC)在促进脑缺血后的损伤修复中的作用及其机制。着重阐明CXCL12基因修饰的EPC 1)对促进大脑中动脉缺血小鼠神经功能恢复的作用,并利用同步辐射活体影像评价功能性血管新生;2)在组织水平上对神经再生和血管新生以及白质损伤修复的作用;3)条件性培养液和外泌体对培养的EPC、神经干细胞以及少突胶质细胞前体细胞的增殖、迁移和分化的影响及关键作用机制。研究结果将对探索缺血性卒中的新型疗法有重要意义。
英文摘要
The applicant had made several progresses in the study of neurovascular regeneration after ischemic stroke. In recent years, my team identified the differential function of chemokine CXCL12 (also known as SDF1) in different phases after stroke. Based on our knowledge about its differential function in the acute and recovery phase, we explored pharmacological small molecule therapy and gene therapy strategies for intervention and acquired positive data. In the past three years I have published 32 peer-reviewed SCI journal articles in leading journals such as . These articles have an accumulated impact factor of more than 140. As the second team member, I received Second Class Science and Technology Progress Award by the Ministry of Education..Based on our previous findings, I propose to further study the function and mechanism of CXCL12 gene modified endothelial progenitor cells (EPC) in promoting brain repair and neurological recovery after ischemic injury, with a focus of the recovery phase. The specific aims are: 1) to investigate the function of CXCL12 gene modified EPC in promoting neurological recovery in mice model of ischemic stroke; at the same time use synchrotron radiation based high-resolution angiography to evaluate functional angiogenesis in living animals. 2) to elucidate the function of CXCL12 gene modified EPC in enhancing neurogenesis, angiogenesis and white matter repair; 3) to explore and characterize the effects of CXCL12-EPC conditioned medium and exosomes on the proliferation, migration, and differentiation of cultured EPC, neural stem cells, and oligodendrocyte progenitor cells. Our findings will provide valuable data to develop novel therapeutics for ischemic stroke.
