CEREBRAL ISCHEMIA DURING ANESTHESIA AND SURGERY

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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.