脑血管疾病是严重危害人类生命与健康的常见病和多发病，但其损伤后神经功能的修复与调控机理尚不清楚。神经干细胞(NSCs)不仅可作为治疗脑缺血再灌注损伤(IRI)的种子细胞，还可作为基因治疗IRI的很好载体。Wnt/β-catenin信号是NSCs增殖调控的重要途径之一。前期我们已证实，noggin能促进衰老小鼠海马NSCs的增殖与增强记忆力。据此，我们推测NSCs增殖可能与Wnt/β-catenin信号通路的调控有关。本课题拟将noggin 基因转染体外培养的大鼠NSCs，再经侧脑室移植入大鼠脑内。通过noggin 基因的原位表达，促进内源性神经的发生、补充损伤丢失的神经元。观察基因修饰NSCs在海马与缺血半影区的增殖、分化与迁移规律；最后检测Wnt/β-catenin信号通路在对noggin修饰NSCs增殖、分化与迁移的调控机制，为临床应用NSCs移植治疗IRI调控提供理论依据

Cerebrovascular disease frequently occuring in central nerve system causes serious damage to human life, but the mechanism underlying neurological repair and regulation after injury remains incompletely known. Current evidences showed neural stem cells (NSCs) not only emerged as potential seeding cells for the cerebral ischemia reperfusion injury (IRI), but could acte as carrier for gene therapy. Wnt/β-catenin signal was one of the important ways for proliferation and regulation of NSCs. Our previous study has confirmed noggin gene was implicated in promoting proliferation of hippocampus NSCs and improving behaviors, suggesting NSCs proliferation may be associated with Wnt/β-catenin signaling pathway. In this study, we attempt to deliver noggin gene into cultured rat NSCs. Transplantation of transected NSCs into the rat lateral ventricle after IRI with in situ expression of noggin gene promotes endogenous neurogenesis, promotes the differentiation of neurons and oligodendrocytes，and compensates the neuron loss after injury. We examine the proliferation, differentiation and migration of transfected NSCs in the ischemic penumbra, meanwhile detect Wnt-1、Axin and BMP expression before and after transplantation, to explore the mechanism that Notch signaling regulates transfected NSCs proliferation, differentiation and migration, as well as to pave the way for clinical application of NSCs transfected with noggin gene in IRI treatment.