BRAIN MICROCIRCULATION AND ENDOTHELIAL INJURY

无内皮剥脱的微血管损伤是由 两种不同的技术（1）使用汞灯的光/染料技术 和血管内荧光素钠（2）He-Ne激光， 埃文的蓝色。 即使没有内皮剥脱， 产生局部血小板聚集并改变血小板的张力（直径）。 微血管损伤 内皮损伤也改变了正常的 乙酰胆碱对收缩的扩张作用。 后者表明， 干扰内皮依赖性舒张因子（EDRF）， 证明了大脑中可能存在这种因素 微血管 刚才描述的影响是在软脑膜血管监测， 使用活体显微镜观察小鼠。 负责地方 血小板聚集和改变的音调将使用 与以下物质相互作用的药理学探针： 环氧化酶-前列腺素-血栓烷途径，伴前列环素，伴 脂肪氧合酶，有钙通道。 我们将尝试模拟 使用产生自由基或血栓素的物质造成的损伤。 我们也将 结合内皮依赖性舒张因子在血管内皮细胞中的表达， 微循环，通过分析因素的性质， 使用药理学探针。 最后，在因素分析中， 在内皮损伤时干扰血小板聚集， 我们将分别研究体外血小板聚集和血管壁 使用电子显微镜。 这些后期研究将开始确定 是否影响体内血小板反应的药物， 或者他们是否在改变血小板， 血管壁损伤程度。 拟议的研究与以下方面有关： 重要的临床问题，如（1）脑梗死由于小 内皮损伤后的血管阻塞（2） 可能依赖于平滑肌释放的小动脉壁 在增强的血小板聚集过程中促有丝分裂原（据报道， 高血压）（3）内皮损伤后血管反应性改变 在诸如局部缺血、高血压、血管破裂 蛛网膜下腔出血外伤

Microvascular injury, without denudation of endothelium is produced with two different techniques (1) a light/dye technique employing a mercury lamp and intravascular sodium fluorescein (2) a He-Ne laser in the presence of Evan's blue. Even without endothelial denudation the endothelial injury produces local platelet aggregation and alters the tone (diameter) of the injured microvessels. The endothelial injury also changes the normal dilating action of acetylcholine to a constriction. The latter suggests interference with an endothelial dependent relaxing factor (EDRF) and demonstrates the probable existence of such a factor in brain microvessels. The effects just described are monitored in pial vessels of mice using intravital microscopy. The mechanisms responsible for the local platelet aggregation and the altered tone will be investigated using pharmacologic probes interacting with the following: cyclooxygenase-prostaglandin-thromboxane pathway, with prostacyclin, with lipoxygenase, with calcium channels. We will attempt to mimic responses to injury by using agents producing radicals or thromboxane. We also will couple the demonstration of endothelium dependent relaxing factor(s) in the microcirculation, with an analysis of the nature of the factor(s) through the use of pharmacologic probes. Finally, in our analysis of factors interferring with platelet aggregation in response to endothelial injury, we will separately study platelet aggregation in vitro, and vessel walls using electromicroscopy. These latter studies will begin to determine whether drugs that affect the response of platelets in vivo, are actually working on the platelet or whether they are, instead or also, altering the amount of injury at the vessel wall. The proposed studies are relevant to important clinical problems such as (1) cerebral infarction due to small vessel obstruction following endothelial damage (2) hypertrophy of arteriolar walls which might be dependent upon release of smooth muscle mitogens during enhanced platelet aggregation (reported by some to occur in hypertension) (3) altered vascular reactivity following endothelial injury in such diverse conditions as ischemia, hypertension, vascular rupture with subarachnoid hemorrhage, trauma.