BRAIN REPERFUSION INJURY--ENERGY STATE & FREE RADICALS

这项建议的长期目标是：(A)制定一项小型 全脑缺血的动物模型，以及(B)使用该模型测试电流 丹参酮减轻再灌注性脑损伤的假说 药理学手段。这两个目标都直接关系到共同和 脑缺血再灌流的临床重要情况 损伤；例如，心脏骤停伴缺氧性/缺血性脑病。 与这两个目标有关的具体目标( 奖)是：(1)结合微波酶失活技术 和核磁共振(核磁共振)波谱来量化 沙土鼠短期脑缺血中的高能中间体； 测试假设，能源利用率在开始的时候 缺血决定了随后的高能量代谢的恢复。 灌流；(3)体外代谢变化与In的观察 人的体外磷和质子核磁共振波谱 缺血和再灌流；(4)建立评估氧气的方法 自由基产生与形态缺血细胞变化及其相关性 这些测量与大脑的能量状态有关，以及(5)评估 治疗干预措施，如别嘌醇，以防止再发 采用充分发展的灌流损伤动物模型。 这些实验基于重复测量设计；基本的 使用的统计方法是阶乘的方差分析 做实验。 最后一个长期目标是在以下领域获得教学经验 中风和核磁共振在神经学中的应用。这 将通过教授研究生级别的核磁学课程来实现 磁共振和神经科学，并参与临床教学 神经内科的活动。

The long term objectives of this proposal are to: (a) develop a small animal model of global ischemia, and (b) use this model to test current hypotheses concerning reduction of reperfusion brain injury by pharmacologic means. Both objectives are directly related to common and clinically important circumstances of brain ischemia and reperfusion injury; for example, cardiac arrest with hypoxic/ischemic encephalopathy. Specific Aims related to these two objectives (all five years of the award) are: (1) to combine the techniques of microwave enzyme inactivation and nuclear magnetic resonance (NMR) spectroscopy to quantitate changes in high-energy intermediates in short-term cerebral ischemia in gerbils; (2) test the hypothesis that the rate of energy utilization at the onset of ischemia determines subsequent recovery of high-energy metabolism with re- perfusion; (3) relate in vitro metabolic changes to observation of in vitro phosphorous and proton nuclear magnetic resonance spectra in ischemia and re-perfusion; (4) develop methods for assessment of oxygen free radical production and morphologic ischemic cell change and correlate these measures with the energy state of the brain, and (5) assess therapeutic interventions, such as allopurinol, for prevention of re- perfusion injury using the fully developed animal model. The experiments are based on a repeated measures design; the basic statistical method used is analysis of variance for a factorial experiment. A final long term objective is to gain teaching experience in the area of stroke and nuclear magnetic resonance applications in neurology. This will be achieved by teaching graduate level courses in nuclear magnetic resonance and neuroscience, and participating in the clinical teaching activities of the Department of Neurology.