CEREBRAL ISCHEMIA DURING ANESTHESIA AND SURGERY

描述：(改编自申请人的摘要)有一个 发生脑缺血的风险相当大 麻醉和手术，特别是在心脏、神经和 颈动脉手术。麻醉剂可以调节突触活动 因此可以想象，它们可能也会影响 脑缺血的病理生理学和预后。最新数据 已经表明，兴奋性神经递质的释放， 尤其是谷氨酸，以及突触后谷氨酸的刺激 受体在缺血神经元的病理生理学中起重要作用 受伤。这里要评估的假设是，确定 麻醉剂通过减少脑损伤减少缺血性脑损伤 兴奋性毒性。第一个努力将是确定 麻醉剂的保护作用，独立于它们对 大鼠局灶性脑缺血模型的体温调节。实验 确定麻醉药减轻缺血性损伤的机制 将分三个阶段进行。第一个是确定是否 麻醉药通过减少谷氨酸的释放减少兴奋性毒性 在局灶性脑缺血期间。下一阶段是确定是否 麻醉剂减少因直接输注到心脏的损伤。 谷氨酸受体特异性激动剂NMDA和AMPA的大脑。在 第三阶段，麻醉药对皮质扩散性抑制的影响 (CSD)将被确定。

DESCRIPTION: (Adapted from the applicant's abstract) There is a considerable risk of the occurrence of cerebral ischemia during anesthesia and surgery, particularly during cardiac, neurologic and carotid artery surgery. Anesthetic agents can modulate synaptic activity and therefore it is conceivable that they might also influence the pathophysiology of and outcome following cerebral ischemia. Recent data have shown that the release of excitatory neurotransmitters, particularly glutamate, and the stimulation of post-synaptic glutamate receptors play a major role in the pathophysiology of ischemic neuronal injury. The hypothesis that will be evaluated here is that certain anesthetic agents reduce ischemic cerebral injury by reducing excitotoxicity. The first effort will be to determine the magnitude of the protective effects of anesthetics, independent of their effects on thermoregulation, in a rat model of focal cerebral ischemia. Experiments to determine the mechanisms by which anesthetics reduce ischemic injury will be conducted in three phases. The first is to determine whether anesthetics reduce excitotoxicity by reducing the release of glutamate during focal ischemia. The next phase is to determine whether anesthetics reduce injury that is produced by direct infusion into the brain of specific glutamate receptor agonists NMDA and AMPA. In the third phase, the effect of anesthetics on cortical spreading depression (CSD) will be determined.