HEMORHEOLOGICAL FACTORS IN CEREBRAL ISCHEMIA

脑缺血的血液流变学因素

• 批准号: 2264019
• 负责人: MARK J FISHER
• 金额: $ 21.13万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2264019
• 关键词: astrocytes; cell cell interaction; cerebral ischemia /hypoxia; clotting factor; disease /disorder proneness /risk; fibrinolysis; fibrinolytic agents; hemostasis; human tissue; interleukin 1; laboratory mouse; plasminogen activator inhibitors; stroke; tissue /cell culture; tumor necrosis factor alpha; vascular endothelium; vascular smooth muscle nervous control

The purpose of this project is to define hemostatic regulatory mechanisms of the brain. This will be investigated from two-perspectives: an in vitro analysis of the hemostatic effects of astrocyte-endothelial interactions, and an analysis of fibrinolytic proteins in post-mortem brain tissue. The in vitro study will utilize bovine brain capillary endothelial cells grown in monolayers and capillary-like structures, and will define the hemostatic effects of a) soluble factors elaborated by astrocytes and b) direct contact of astrocytes with capillary-like structures. Hemostatic factors to be studied in vitro include thrombomodulin, tissue factor, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1). Analysis of hemostasis factors will use antigenic and functional assays, as well as polymerase chain reaction and in-situ hybridization techniques. Neutralizing antibodies will be used to define the roles of interleukin-l (IL-I) and tumor necrosis factor (TNF) as mediators of astrocyte effects on endothelial hemostasis. The relationship between fibrinolysis and the brain will be further studied using autopsy samples to analyze the regional distribution of endothelial fibrinolytic proteins tPA, urokinase-type plasminogen activator (uPA), and PAI-1. This will be studied in brain from subjects without stroke risk factors, subjects with hypertension, and subjects with diabetes. The relationship between brain fibrinolysis, stroke risk factors, and brain expression of IL-1 and TNF will be defined. Vascular expression of fibrinolytic factors will be quantified using immunocytochemistry and tissue content will be determined by enzyme immunoassay; in-situ hybridization will also be used for localization purposes. Completion of this project will substantially enhance our knowledge of processes relevant to ischemic stroke pathogenesis and lead to new strategies for stroke prevention.

该项目的目的是定义止血调节机制 大脑的。 对此要从两个角度进行考察： 星形胶质细胞-内皮细胞止血作用的体外分析 相互作用，以及死后纤溶蛋白的分析 脑组织。体外研究将利用牛脑毛细血管 以单层和毛细血管样结构生长的内皮细胞，以及 将定义 a) 可溶性因子的止血作用 星形胶质细胞和 b) 星形胶质细胞与毛细血管样直接接触 结构。 体外研究的止血因素包括 血栓调节蛋白、组织因子、组织纤溶酶原激活剂 (tPA) 和 纤溶酶原激活剂抑制剂-1 (PAI-1)。 止血因素分析 将使用抗原和功能测定以及聚合酶链 反应和原位杂交技术。 中和抗体 将用于定义白细胞介素-1 (IL-I) 和肿瘤的作用 坏死因子（TNF）作为星形胶质细胞对内皮细胞影响的介质 止血。纤维蛋白溶解与大脑的关系 进一步研究使用尸检样本来分析区域分布 内皮纤溶蛋白 tPA、尿激酶型纤溶酶原 激活剂（uPA）和 PAI-1。 这将在受试者的大脑中进行研究 无中风危险因素的受试者、患有高血压的受试者以及患有以下疾病的受试者 糖尿病。脑纤维蛋白溶解与中风风险之间的关系 因素，以及 IL-1 和 TNF 的脑表达将被定义。 血管 纤溶因子的表达将使用量化 免疫细胞化学和组织含量将通过酶测定 免疫测定；原位杂交也将用​​于定位 目的。该项目的完成将大大增强我们的 了解与缺血性中风发病机制和铅相关的过程 预防中风的新策略。