约1/3脑卒中幸存者落下残疾，神经再生有望帮助残疾功能的恢复，而神经再生依赖于与血管新生之间的协同共生。因此，只有促进"血管新生-神经再生"之间的协同共生作用，才能保证脑卒中后的功能修复。 HSPA12B是新发现的促血管生成因子。我们前期实验发现，高表达HSPA12B可加速脑卒中小鼠的功能恢复、增加新生神经元数量，提示HSPA12B有可能通过促进"血管新生-神经再生"协同共生而促进脑卒中后功能恢复。 为此，本项目拟采用HSPA12B转基因鼠、基因敲除鼠制备脑卒中模型，综合评价不同表达水平的HSPA12B对脑卒中后功能障碍恢复的影响，并结合"血管内皮细胞-神经祖细胞"共培养模型，探讨eNOS-BDNF信号在HSPA12B促进"血管新生-神经再生"协同共生中的作用。研究结果将为发现脑卒中后功能恢复的干预靶点奠定基础。 本项目是2013年即将结题的国家自然基金的延续性、纵深性研究。

One-third of stroke survivors suffer from disability, which could be relieved by neurogenesis. Neurogenesis is regulated by the coupling of "angiogenesis-neurogenesis", however, no effective treatment is available for this purpose in clinic. Thus, it is important to identify targets for regulating the coupling of "angiogenesis-neurogenesis" which in turn to repair the disability due to stroke. HSPA12B is a newly discovered proangiogenic factor. Our preliminary data demonstrate that overexpression of HSPA12B promotes the post-stroke function recovery and increases the number of new neurons in mice, suggesting that overexpression of HSPA12B could promote the post-stroke function recovery through upregulating the coupling of "angiogenesis-neurogenesis". We will thoroughly evaluate the effect of HSPA12B on post-stroke function recovery using HSPA12B transgenic mice and knockout mice. We will also examine whether HSPA12B upregulates the coupling of "angiogenesis- neurogenesis" in ischemic brains. By using coculture model of endothelial cells and neural progenitor cells, we will investigate the roles of eNOS-BDNF signaling in HSPA12B-promoted coupling of "angiogenesis- neurogenesis". The results will provide norvel potential targets for management and treatment of post-stroke disability.