CEREBRAL MICROCIRCULATION IN EXPERIMENTAL BRAIN INJURY

实验性脑损伤中的脑微循环

• 批准号: 2263568
• 负责人: HERMES A KONTOS
• 金额: $ 20.91万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-04-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2263568
• 关键词: NMDA receptors; amine oxidoreductase; blood brain barrier; brain injury; carbon dioxide; cats; cerebral ischemia /hypoxia; cold temperature; cytoskeletal proteins; free radical oxygen; hydroxyl radical; microcirculation; neuroprotectants; nitric oxide; oxidative stress; potassium channel; reperfusion; superoxides; vasodilatation; vasodilators

The long-range aim of this proposal is to establish the role and mechanism of action of oxygen radicals in the vascular injury which occurs in fluid-percussion brain injury and during reperfusion following brain ischemia. In the preceding funding periods of this project we established that oxygen radicals are generated after fluid-percussion brain injury and during reperfusion following global ischemia. In the present proposal we plan to identify the mechanisms of the cerebral arteriolar vasodilation induced by superoxide, hydrogen peroxide and hydroxyl radical. Specifically, we will investigate the role of activation of guanylate cyclase and the activation of ATP-sensitive potassium channels. We will also investigate the mechanism by which oxygen radicals interfere with endothelium-dependent relaxation. These studies will target the identification of the chemical identity of endothelium-derived relaxing factor (EDRF) and examination of whether oxygen radicals stimulate increased generation of release of EDRF and whether peroxynitrite is formed by the interaction of nitric oxide and superoxide and eventually generates hydroxyl radical. We will also attempt to distinguish between hydroxyl radical generated via production of peroxynitrite from hydroxyl radical generated via the iron-catalyzed Haber-Weiss reaction. Other studies will investigate the mechanism of the abnormal response to CO2 in fluid-percussion injury and in ischemia/reperfusion. We will investigate the role of nitric oxide synthase-mediated effects and the role of activation of ATP-sensitive potassium channels. the mechanism of the cytoskeletal abnormalities in the breakdown of the blood-brain barrier induced by oxygen radicals will be evaluated with respect to the possible role of cytoskeletal contractile proteins and the role of phagocytic cells. Finally, we will investigate whether small reductions in temperature or blockade of the NMDA receptor are beneficial in brain injury and ischemia because they cause changes in the generation of oxygen radicals.

这项建议的长远目标是确立联合国的作用， 氧自由基在血管损伤中的作用机制， 发生在液压冲击脑损伤和再灌注期间， 脑缺血 在本项目的前几个资助期内， 确定了在流体冲击后产生氧自由基 脑损伤和全脑缺血后再灌注期间。 在 目前的建议，我们计划确定大脑的机制， 超氧化物、过氧化氢和 羟基自由基 具体来说，我们将研究 鸟苷酸环化酶的激活和ATP敏感的 钾离子通道 我们还将研究 氧自由基干扰内皮依赖性舒张。 这些 研究的目标是确定 内皮源性舒张因子（EDRF）和检查是否 氧自由基刺激EDRF释放的产生增加， 过氧亚硝酸盐是否是由一氧化氮和 超氧化物并最终产生羟基自由基。 我们还将 试图区分通过生产产生的羟基自由基 过氧亚硝酸根的羟基自由基产生的铁催化 Haber-Weiss反应 其他研究将调查的机制， 液压冲击伤和颅脑损伤对CO2异常反应 缺血/再灌注 我们将研究一氧化氮的作用 腺苷酸酶介导的作用和激活ATP敏感的 钾离子通道 细胞骨架异常的机制， 由氧自由基引起的血脑屏障的破坏将 评价细胞骨架的可能作用 收缩蛋白和吞噬细胞的作用。 最后我们将 研究是否温度的小幅度降低或 NMDA受体在脑损伤和缺血中是有益的，因为它们 引起氧自由基生成的变化。