CEREBRAL ISCHEMIA DURING ANESTHESIA AND SURGERY

描述：（改编自申请人的摘要）有一个 脑缺血发生的风险相当大， 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，它们也可能影响 脑缺血后的病理生理学和结果。最近的数据 已经表明兴奋性神经递质的释放， 特别是谷氨酸，以及突触后谷氨酸的刺激 受体在缺血性神经元损伤的病理生理学中起主要作用， 损伤这里要评估的假设是， 麻醉剂通过减少缺血性脑损伤 兴奋性毒性第一项工作将是确定 麻醉剂的保护作用，独立于其对 温度调节，在大鼠局灶性脑缺血模型。实验 确定麻醉剂减少缺血性损伤的机制 将分三个阶段进行。第一，确定是否 麻醉剂通过减少谷氨酸的释放来减少兴奋性毒性 在局部缺血期间。下一阶段是确定是否 麻醉剂减少了直接输注到 脑内特异性谷氨酸受体激动剂NMDA和AMPA。在 第三阶段，麻醉剂对皮层扩散性抑制的影响 (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.