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CEREBRAL MICROCIRCULATION IN EXPERIMENTAL BRAIN INJURY

实验性脑损伤中的脑微循环

基本信息

批准号：
2891615
负责人：
HERMES A KONTOS
金额：
$ 24.13万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-04-01 至 2000-12-31
项目状态：
已结题

项目摘要

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.

该提案的长期目标是确立角色和氧自由基在血管损伤中的作用机制发生在液体冲击性脑损伤和随后的再灌注过程中脑缺血。在该项目的前期资助期间，我们确定流体冲击后产生氧自由基脑损伤和全身缺血后的再灌注期间。在目前的提案我们计划确定大脑的机制超氧化物、过氧化氢等引起的小动脉血管舒张羟基自由基。具体来说，我们将调查鸟苷酸环化酶的激活和 ATP 敏感的激活钾通道。我们还将研究其机制氧自由基干扰内皮依赖性松弛。这些研究的目标是鉴定化学特性内皮源性舒张因子（EDRF）并检查是否氧自由基刺激 EDRF 释放的增加和过氧亚硝酸盐是否是由一氧化氮和一氧化氮相互作用形成的超氧化物并最终产生羟基自由基。我们还将尝试区分生产过程中产生的羟基自由基由铁催化产生的羟基自由基生成过氧亚硝酸盐哈伯-韦斯反应。其他研究将探讨其机制液体冲击损伤和脑损伤中对 CO2 的异常反应缺血/再灌注。我们将研究一氧化氮的作用合成酶介导的作用和 ATP 敏感激活的作用钾通道。细胞骨架异常的机制氧自由基引起的血脑屏障的破坏将评估细胞骨架的可能作用收缩蛋白和吞噬细胞的作用。最后，我们将调查温度是否小幅降低或封锁 NMDA 受体对脑损伤和缺血有益，因为它们引起氧自由基产生的变化。