The Role of SDF-1 Cerebral Repair Following Stroke

SDF-1 在中风后大脑修复中的作用

• 批准号: 7276788
• 负责人: Aisha Lanette Walker
• 金额: $ 0.79万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-24 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7276788
• 关键词: Adult; Area; Behavioral; Biological Assay; Blood Vessels; Blood flow; Bone Marrow; Brain; Cause of Death; Cell Differentiation process; Cell Proliferation; Cells; Cerebrum; Control Animal; Control Groups; Data; Development; Down-Regulation; Endothelial Cells; Fellowship; Green Fluorescent Proteins; Homing; Hour; Hypoxia; In Vitro; Individual; Injury; Ischemia; Ischemic Stroke; Lead; Mediating; Migration Assay; Modeling; Motor; Mus; Names; Patients; Play; Process; Rate; Recovery of Function; Regulation; Role; Site; Stem cells; Stroke; Stromal Cell-Derived Factor 1; Structure; Testing; Thinking; Tissues; Tube; Up-Regulation; Vascular blood supply; Walkers; angiogenesis; brain tissue; cell motility; cell type; day; disability; mortality; neovascularization; novel; repaired; response; vasculogenesis

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.

描述(申请人提供)：中风是美国第三大致死原因，也是导致长期残疾的首要原因。初步数据显示，在脑修复过程中，基质细胞衍生因子-1(SDF-1)在小鼠脑内表达上调。SDF-1被认为对许多类型的细胞具有趋化作用，并促进血管生成。我推测SDF-1的上调是由于缺氧引起的，并通过诱导新生血管形成和将骨髓来源的细胞归巢到损伤部位来介导脑缺血后的修复机制，从而全面促进功能恢复。为了验证我的假设，我计划：(1)确定SDF-1对脑血管生成的贡献，并使用新型的GFP嵌合小鼠中风模型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血管生成；(3)研究SDF-1在体外是否受到HIF-1调控。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，这可能会降低死亡率并限制中风患者的长期残疾。