BRAIN REPERFUSION INJURY--ENERGY STATE & FREE RADICALS

这项建议的长远目标是：（a）发展一个小型的 全脑缺血的动物模型，和（B）使用该模型测试电流 关于减少再灌注脑损伤的假说 药理学手段。 这两个目标直接关系到共同和 脑缺血再灌注临床重要情况 损伤;例如，伴有缺氧/缺血性脑病的心脏骤停。 与这两个目标有关的具体目标（ 主要有：（1）将微波灭酶技术与联合收割机 和核磁共振（NMR）光谱来定量 沙鼠短期脑缺血中的高能中间体;（2） 测试的假设，即能源利用率在开始的 局部缺血决定了随后的高能量代谢的恢复， 灌注;（3）将体外代谢变化与体内 体外磷和质子核磁共振谱 缺血和再灌注;（4）发展氧评估方法 自由基产生与缺血细胞形态学改变及其相关性 这些措施与大脑的能量状态，和（5）评估 治疗性干预，如别嘌呤醇，以防止再- 灌注损伤使用充分发展的动物模型。 实验是基于重复测量设计;基本的 使用的统计方法是因子方差分析 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病学中的应用。 这 将通过教授研究生水平的课程，在核磁 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.