目前，神经干细胞（NSCs）在缺血后神经细胞再生及神经组织修复中的作用已经成为生命科学领域研究的热点之一。然而，由于 NSCs归巢率低且无法适应脑梗死区微环境而死亡，难以达到预期的治疗效果。前期研究发现lncRNA HOTAIR在脑梗死中显著升高且能诱导NSCs向脑梗死区迁移，提示HOTAIR在NSCs缺血后神经细胞再生及神经组织修复中可能发挥重要的调节作用。项目组进一步筛选出其潜在靶分子miRNA-9及下游的信号通道蛋白CXCR4。基于以上研究，我们推测HOTAIR是NSCs移植治疗缺血性脑损伤关键靶点。为证实这一假说，项目组首次以HOTAIR为靶点，应用慢病毒基因过表达和基因沉默技术，采取细胞生物学和分子生物学相结合的方法，从分子、细胞、动物多层次系统阐明HOTAIR/miRNA-9/CXCR4信号转导通路在调控NSCs生物学行为中的作用，为NSCs治疗缺血性脑损伤提供新思路、新靶点。

Nowadays, many researchers devote to studying cerebral regeneration and repairing insulted cerebral tissue with neural stem cells (NSCs). The experimental and preclinical studies showed that NSCs have the ability of differentiating into neurons, promoting angiogenesis, and integrating and restoring neural pathways to restore the function of damaged parts of the brain. However, it is difficult to achieve the desired results of NSCs treatment for ischemic stroke because most of NSCs are not able to migrate into the infarct zone of brain. How to improve the migration rate of NSCs has become the key issue and must be solved before clinical applications. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are crucial for normal NSCs self-renewal and cellular differentiation, but how lncRNAs gene expression is controlled by the key transcriptional regulators of NSCs has not been clearly established. Till now, no studies have focused on the role of lncRNA HOTAIR in promoting migration and inhibiting apoptosis effects of NSCs after transplantation. Our previous study demonstrated that overexpression of HOTAIR in NSCs could reduce apoptosis and promote the migration of NSCs via targeting miRNA-9/CXCR4 cell signaling pathway in hypoxic condition. So, we hypothesize that up-regulation of HOTAIR in NSCs plays an important role in the regulation of NSCs survival and migration in brain infarction ischemic stroke area. To confirm this hypothesis, we will establish a mouse brain ischemia model and reveal the effects of HOTAIR in NSCs in treatment of ischemia cerebral damage via the combination of cellular biological techniques and molecule biological methods. It is reasonable to speculate that HOTAIR, the novel but practical regulator of NSCs transplantation for ischemic brain damage, introduces a promising strategy for the treatment of ischemic stroke patients.