MICROMETABOLISM OF SELECTIVE BRAIN ISCHEMIC INJURY

缺血性脑损伤的发病机制尚不清楚。我计划这样做 对异常微生理学的级联进行详细分析 在缺血和再循环期间发生的活动，这一过程 重要的临床后果。实验性中风研究的结果 提示要么是乳酸酸中毒，要么是细胞钙紊乱 动态平衡可能是缺血性脑损伤的根本原因。 然而，几乎没有直接证据来证实这些假定的角色 乳酸盐和钙。一种重复性较好的重症前脑模型 本实验室开发的缺血将用于这项研究。工作 该模型显示了空间和空间中神经元的选择性脆弱性 时间到了。损伤的组织学证据持续了几天。 对特定离子、气体或有机化学品敏感的微电极 (微型传感器)将被用来检验这一假说 可以检测到离子和代谢物动态平衡的重要局部变化 并与选择性的脆弱性存在因果关系。我们建议测量 并操纵氢和钙的动态平衡及相关变量 对缺血敏感性不同的前脑区域 血液流动的中断。此信息将与 相同区域的组织学和电生理学特征。 现有的H+、K+、Ca++、Na+和Cl-微型传感器将用于 学习。此外，我们还希望开发二氧化碳、氧气、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.