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: 6893215
• 负责人: Aisha Lanette Walker
• 金额: $ 2.58万
• 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 2008-09-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6893215
• 关键词: angiogenesis; behavior test; bone marrow; brain circulation; cell differentiation; cell migration; cell proliferation; cerebral ischemia /hypoxia; chemokine; disease /disorder model; functional ability; gene expression; genetically modified animals; human tissue; immunocytochemistry; laboratory mouse; neuroprotectants; predoctoral investigator; stroke therapy; vascular endothelium

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（由申请人提供）：中风是美国第三大死亡原因，也是长期残疾的主要原因。初步数据表明，在大脑修复过程中，基质细胞衍生的因子1（SDF-1）在小鼠的大脑中被上调。 SDF-1被认为是许多细胞类型的趋化性，并促进血管生成。我假设SDF-1的上调是由于缺氧引起的，并通过诱导新的临床化和将骨髓衍生的细胞归因于损伤部位，从而介导大脑的修复机制，从而导致功能恢复的总体增加。为了检验我的假设，我计划：（1）确定SDF-1对大脑新生血管的贡献，并使用新型的GFP嵌合小鼠中风模型确定功能恢复后的功能恢复后的增加，（2）SDF-1确定是否通过上调血管生成的作用来诱导效率上的效率（3），（3缺氧在体外受到HIF-1调节状态。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，从而降低死亡率并限制中风患者的长期残疾。