MICROMETABOLISM OF SELECTIVE BRAIN ISCHEMIC INJURY

缺血性脑损伤的发病机制知之甚少。 我计划 进行详细分析的级联异常微生理 活动发生在缺血和再循环，一个过程， 重要的临床后果。 实验性卒中研究结果 提示乳酸酸中毒或细胞钙破坏 体内平衡可能是缺血性脑损伤的根本原因。 然而，几乎没有直接证据证实这些假设的作用 乳酸盐和钙 一种高度可重复的重度前脑损伤模型 在本研究中将使用在该实验室中形成的缺血。 工作 这个模型显示了空间神经元的选择性脆弱性， 时间 损伤的组织学证据持续数天。 对特定离子、气体或有机化学品敏感的微电极 （微传感器）将用于测试假设， 可以检测到离子和代谢物体内平衡的重要局部变化 与选择性脆弱性有因果关系。 我们建议测量 并控制氢和钙的体内平衡和相关变量 在对缺血敏感性不同的前脑区域， 血液流动的中断。 这些信息将与 相同区域的组织学和电生理学表征。 现有的用于H+、K+、Ca++、Na+和Cl-的微传感器将用于此。 study. 此外，我们还希望开发用于CO2、O2、乳酸和 葡萄糖

The pathogenesis of ischemic brain injury is poorly understood. I plan to undertake detailed analyses of the cascade of aberrant microphysiological activities that occur during ischemia and recirculation, a process that has important clinical ramifications. Results from experimental stroke rsearch suggest that either lactic acidosis or disruption of cell calcium homeostasis may be fundamentally responsible for ischemic brain injury. However, little direct evidence exists to confirm these postulated roles for lactate and calcium. A highly reproducible model of severe forebrain ischemia developed in this laboratory will be used in this study. Work with this model has shown a selective vulnerability of neurons in space and time. Histological evidence of damage progresses for days. Microelectrodes sensitive to particular ions, gases, or organic chemicals (microsensors) will be used to test the hypothesis that temporally important local changes in ion and metabolite homeostasis may be detected and be causally related to selective vulnerability. We propose to measure and manipulate the hydrogen and calcium homeostasis and related variables in forebrain regions with varying sensitivity to ischemia during and after the interruption of blood flow. This information will be correlated to histological and electrophysiological characterization of the same areas. Existing microsensors for H+, K+, Ca++, Na+, and Cl- will be used in this study. In addition we expect to develop sensors for CO2, O2, lactate, and glucose.