COORDINATE CHANGES IN BRAIN ENERGY METABOLISM AND PROTEIN SYNTHESIS

已经研究了大脑能量代谢和蛋白质合成的变化。 沙土鼠短暂性双侧脑缺血后。项目区域 包括：a)应激或热冲击的持续特征 短暂性脑缺血后的反应；b)机制的评估 负责缺血所致的海马区强啡肽的耗竭； 和c)整体蛋白质合成抑制和恢复的机制 在缺血后。 主要哺乳动物的翻译增加的初步论证 应激蛋白HSP70正被延伸到转录水平。 初步结果表明，HSP70和HSP70的mRNA的诱导 泛素，在沙土鼠体温过高后，使用大鼠cdna探针，以及 现在可以研究缺血的影响了。免疫组织化学 热休克蛋白70的定位是用特异性的单抗进行的 用于诱导蛋白质。 沙土鼠脑内强啡肽A耗竭的早期观察 脑缺血仅局限于海马区。的时间进程 多肽水平的变化与酶活性的增强一致 缺血后含强啡肽的齿状颗粒细胞。这些 结果将海马区易损性的概念扩展到 神经化学水平，并提示内源性海马区的作用 兴奋性毒性机制在海马CA1区缺失机制中的电路机制 缺血后的神经元。

Changes in brain energy metabolism and protein synthesis have been studied following transient bilateral ischemia in the gerbil. Project areas include: a) continued characterization of the stress or heat shock response following transient ischemia; b) evaluation of mechanisms responsible for the ischemia-induced depletion of hippocampal dynorphin; and c) mechanisms of overall protein synthesis inhibition and recovery following ischemia. The initial demonstration of increased translation of the major mammalian stress protein, hsp 70, is being extended to the transcriptional level. Preliminary results demonstrate the induction of mRNA's for hsp 70 and ubiquitin, using rat cDNA probes, following hyperthermia in the gerbil, and the effects of ischemia can now be investigated. Immunohistochemical localization of hsp 70 is being pursued with monoclonal antibodies specific for the induced protein. An earlier observation of dynorphin A depletion in gerbil brain following ischemia has been localized exclusively to hippocampus. The time course of changes in peptide levels is consistent with increased activity of the dynorphin-containing dentate granule cells following ischemia. These results extend the concept of hippocampal vulnerability to the neurochemical level, and suggest a role for the intrinsic hippocampal circuitry in proposed excitotoxic mechanisms for loss of hippocampal CA1 neurons following ischemia.