The Role of SDF-1 Cerebral Repair Following Stroke

描述（由申请人提供）：中风是美国第三大死亡原因，也是导致长期残疾的主要原因。初步数据显示，在大脑修复过程中，小鼠大脑中基质细胞衍生因子-1 （SDF-1）表达上调。SDF-1被认为对许多细胞类型具有趋化作用，并促进血管生成。我假设SDF-1的上调是由于缺氧引起的，并通过诱导新生和将骨髓来源的细胞归巢到损伤部位，从而介导脑缺血后的修复机制，从而导致功能恢复的总体增加。为了验证我的假设，我计划：(1)利用一种新型的GFP嵌合小鼠中风模型确定SDF-1对大脑新生血管的贡献，并确定缺血后功能恢复的增加；(2)确定SDF-1在体外是通过上调血管生成还是通过上调血管生成来诱导新生血管；(3)研究体外缺氧时SDF-1的上调是否受到HIF-1的调节。了解中风后的内源性修复机制可能会导致新的治疗方法来增强自然修复过程，这可能会降低中风患者的死亡率和限制长期残疾。

DESCRIPTION (PROVIDED BY APPLICANT): Stroke is the nation's third leading cause of death and the leading cause of long-term disability. Preliminary data show that during cerebral repair, Stromal Cell-Derived Factor-1 (SDF-1) is upregulated in the brain of mice. SDF-1 is thought to be chemotactic for many cell types, and to promote angiogenesis. I hypothesize that the upregulation of SDF-1 is due to hypoxia and mediates the repair mechanisms of the brain following ischemia by inducing neovsacularization and by homing bone marrow derived cells to the site of injury leading to an overall increase in functional recovery. To test my hypothesis, I plan to: (1) determine the contribution of SDF-1 to neovascularization of the brain and determine the increase in functional recovery post-ischemia using a novel GFP chimeric mouse stroke model, (2) determine whether SDF-1 induces neovascularization in vitro by upregulating angiogenesis or by upregulating vasculogenesis, (3) investigate whether the upregulation of SDF-1 in response to hypoxia is under HIF-1 regulation in vitro. Understanding the endogenous repair mechanisms following stroke could lead to novel treatments to enhance the natural repair processes, which could decrease mortality and limit long-term disability seen in stroke patients.