HYPOXIA OF BRAIN TISSUE SLICES

本课题旨在研究急性脑损伤的病理生理学。 低氧，以及暴露在低氧环境中的后遗症。其意图是 发现氧气不足本身的影响，有别于 脑循环改变所介导的效应。 脑组织切片将在体外保持并暴露于 不同程度和持续时间的缺氧。这些条件将在中定义 发生可逆和不可逆的突触功能改变。 组织pH和其他离子浓度将通过离子选择来测量 微电极。组织的氧分压将通过极谱测定。膜 可逆性和不可逆性受损神经元的特性将是 通过细胞内方法和电压钳制来确定。的角色 离子、pH和缺氧后过量氧化剂对回收率的影响 将会被研究。营养素、代谢物可能的保护作用 以及针对缺氧性损害的药物将被确定。体外研究结果 将与实验中对完整大脑的观察进行比较 与西尔维娅博士合作完成。间质缺氧性改变 离子的电生理功能将与生化有关 改变。暴露在低氧环境中的慢性后遗症也将是 学习。严重但短暂的氧气引起的神经元功能改变 剥夺将被确定，并可能适应长时间的， 中度缺氧。

This project is designed to study the pathophysiology of acute cerebral hypoxia, as well as the aftereffects of exposure to hypoxia. The intent is to discover the effect of oxygen insufficiency itself, as distinct from effects mediated by changes of cerebral circulation. Slices of cerebral tissue will be maintained in vitro and exposed to hypoxia of varying degree and duration. The conditions will be defined in which reversible and irreversible changes of synaptic function occur. Tissue pH and other ion concentrations will be measured with ion selective microelectrodes. Tissue pO2 will be determined by polarography. Membrane properties of reversibly and irreversibly impaired neurons will be determined by intracellular methods and by voltage clamping. The roles of ions, of pH, and of post-hypoxic excess oxidant in influencing recovery will be studied. The possible protective effect of nutrients, metabolites and drugs against hypoxic damage will be determined. Findings in vitro will be compared with observations on intact brains in experiments performed in cooperation with Dr. Sylvia. Hypoxic changes of interstitial ions and of electrophysiological function will be related to biochemical changes. The chronic aftereffects of exposure to hypoxia will also be studied. Altered neuronal function caused by severe but transient oxygen deprivation will be determined as well as possible adaptation to prolonged, moderate lack of oxygen.