MICROMETABOLISM OF SELECTIVE BRAIN ISCHEMIC INJURY

缺血性脑损伤的发病机制尚不清楚。 我计划 undertake detailed analyses of the cascade of aberrant microphysiological 缺血和再循环期间发生的活动，这一过程 重要的临床影响。 实验性中风研究结果 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. 高度可重复的严重前脑模型 本研究将使用该实验室中发生的缺血。 工作 with this model has shown a selective vulnerability of neurons in space and 时间。 Histological evidence of damage progresses for days. Microelectrodes sensitive to particular ions, gases, or organic chemicals （微传感器）将用于检验暂时的假设 可以检测到离子和代谢物稳态的重要局部变化 and be causally related to selective vulnerability. We propose to measure 并操纵氢和钙的稳态及相关变量 in forebrain regions with varying sensitivity to ischemia during and after 血流中断。 该信息将与 histological and electrophysiological characterization of the same areas. 现有的 H、K、Ca、Na 和 Cl- 微传感器将用于此 研究。 此外，我们预计开发 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.