BRAIN MICROCIRCULATION AND ENDOTHELIAL INJURY

我们的长期目标是扩大我们的知识有关的机制 调节大脑微循环 这些机制至关重要 为大脑提供适当的流量，其功能尤其是 对氧气和营养输送受损敏感。 本研究 关注内皮在控制小动脉直径中的作用， 内皮损伤会扰乱血流的方式。 两组 研究计划。 所有这些都是相对独特的，因为它们是在 对体内微循环的影响 小鼠大脑表面的小动脉 通过活体显微镜观察。 第一组研究调查了 内皮细胞在产生舒张或收缩因子中的作用 （EDRF，EDCF），当被选择性血管活性激动剂刺激时或在 血压升高的自动调节。 内皮损伤， 由氦氖激光/伊文思蓝原位产生的激光束引起聚焦损失， 生产EDRF或EDCF的能力，并提供了一种测试方法， 激动剂的作用依赖于这种内皮机制。 将使用药理学探针，然后进行化学测量， 确定内皮衍生介质的化学性质（例如， 前列腺素类、其它类花生酸类）。 我们还将使用药理学探针， 确定蛋白激酶C和鸟苷酸或腺苷酸的作用 环化酶和L-精氨酸介导的合成，释放或影响 内皮衍生介质。 第二组研究涉及 血管内皮损伤引起的血小板聚集 小动脉 药理学探针将用于研究改变的 抗聚集内皮衍生舒张因子的合成/释放 在由以下物质损伤的部位促进局部血小板粘附/聚集 光/染料。 在这样的部位捕获栓塞的血小板将是有利的。 研究了其与短暂性缺血性脑卒中的重复症状的相关性 攻击药理学探针将用于评估增加的 当流动时释放这种EDRF以减少血小板聚集， 剪切力增加。 L-精氨酸在调节细胞凋亡中的作用 这种EDRF的抗聚集和抗粘附性能将是 研究了

Our long term goals are to expand our knowledge concerning mechanisms regulating brain microcirculation. These mechanisms are vitally important in providing appropriate flow to the brain, whose function is especially sensitive to impaired delivery of oxygen and nutrients. Present studies focus on the role of endothelium in controlling diameter of arterioles, and on the ways in which endothelial damage can derange flow. Two groups of studies are planned. All are relatively unique because they are conducted on microcirculation in vivo. Surface arterioles on the mouse brain are observed by intravital microscopy. The first group of studies investigates the role of endothelium in producing relaxing or constricting factors (EDRFs, EDCFs) when stimulated by selective vasoactive agonists or during autoregulation to an increase in blood pressure. Endothelial injury, produced in situ by helium neon laser/Evans blue causes a focus of lost capacity to produce EDRFs or EDCFs and provides a method for testing which agonists are dependent upon such an endothelial mechanism for their action. Pharmacologic probes, followed by chemical measurements will be used to determine the chemical nature of the endothelium derived mediators (e.g. prostanoids, other eicosanoids). We will also use pharmacologic probes to determine the role of protein kinase C, and of guanylate or adenylate cyclase and of L-arginine in mediating the synthesis, release or effects of the endothelium derived mediators. The second group of studies concerns the production of platelet aggregation by endothelial injury in the arterioles. Pharmacologic probes will be used to study the role of altered synthesis/release of an antiaggregant endothelium derived relaxing factor in promoting local platelet adhesion/aggregation at a site injured by light/dye. The capture of embolizing platelets at such a site will be studied for its relevance to repetitive symptoms of transient ischemic attacks. Pharmacologic probes will be used to assess the role of increased release of such an EDRF in decreasing platelet aggregation when flow and shear are increased. The role of L-arginine in regulating the antiaggregating and antiadhesive properties of this EDRF will be investigated.