CEREBRAL MICROCIRCULATION IN EXPERIMENTAL BRAIN INJURY

实验性脑损伤中的脑微循环

• 批准号: 3399340
• 负责人: HERMES A KONTOS
• 金额: $ 16.31万
• 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 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3399340
• 关键词: NADPH cytochrome c2 reductase; arachidonate; blood brain barrier; bradykinin; brain circulation; brain injury; cats; cerebral artery; cerebrovascular disorders; cytochrome P450; electron microscopy; enkephalins; fatty acid metabolism; free radicals; histology; hypocapnia; laboratory rabbit; lipoxygenase; membrane channels; microcirculation; oxygen consumption; prostaglandin endoperoxide synthase; substance P; superoxides; vascular endothelium permeability; vascular smooth muscle; vasoconstriction; vasodilatation; xanthine oxidase

The objectives of these studies are to clarify the mechanism of the cerebral microcirculatory alterations following experimental fluid-percussion brain injury in anesthetized cats and in rabbits. This type of brain injury induces pial arteriolar dilation associated with a reduced responsiveness to the vasoconstrictor effects of arterial hypocapnia and with disturbed autorregulatory dilation in response to arterial hypotension. The vessels which showed these abnormalities have lesions in their vascular smooth muscle and endothelium, and display reduced oxygen consumption. The proposed studies will test the hypothesis that these abnormalities are mediated by free oxygen radicals generated in association with accelerated arachidonate metabolism via cyclooxygenase. The proposed experiments are designed to identify the factors which influence superoxide anion radical generation after brain injury, to determine whether superoxide anion radical generated by brain injury traverses the cell membrane via the anion channel, to identify the enzymatic sources of superoxide, including cyclooxygenase, lipoxygenase, cytochrome P450 reductase and xanthine oxidase, to examine whether substance P, enkephalins or bradykinin initiate the sequence which leads to superoxide production, to examine the effects of oxygen radicals on the blood-brain barrier and to determine whether endothelium-dependent vasodilator reponses are disturbed after brain injury.

这些研究的目的是阐明 脑微循环改变 麻醉猫和兔子的液压冲击脑损伤。 这 一种类型的脑损伤诱导软脑膜小动脉扩张， 降低对动脉血管收缩作用的反应性 低碳酸血症，并伴有对 动脉低血压 显示这些异常的血管 血管平滑肌和内皮损伤，并显示 减少氧气消耗。 拟议中的研究将检验这一假设 这些异常是由体内产生的氧自由基介导的， 与通过环氧合酶加速花生四烯酸代谢有关。 所提出的实验旨在确定 影响脑损伤后超氧阴离子自由基产生， 确定脑损伤是否产生超氧阴离子自由基 通过阴离子通道穿过细胞膜，以识别 过氧化物的酶源，包括环氧合酶，脂氧合酶， 细胞色素P450还原酶和黄嘌呤氧化酶，以检查是否 P物质、脑啡肽或缓激肽启动导致 超氧化物的产生，以检查氧自由基对 血脑屏障，并确定是否内皮依赖性 脑损伤后血管扩张反应紊乱。