CEREBRAL ISCHEMIA DURING ANESTHESIA AND SURGERY

麻醉和手术期间的脑缺血

• 批准号: 2190998
• 负责人: Piyush M Patel
• 金额: $ 10.17万
• 依托单位: VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2190998
• 关键词: NMDA receptors; anesthesia; blood pressure; cerebral ischemia /hypoxia; disease /disorder model; disease /disorder proneness /risk; excitatory aminoacid; gene induction /repression; glutamate receptor; glutamates; histology; in situ hybridization; isoflurane; laboratory rat; molecular pathology; neuropharmacology; pathologic process; pentobarbital; phenylephrine; regulatory gene; surgery; synapses; ultrasound blood flow measurement

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.

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，特别是心脏、神经和手术期间 颈动脉手术。麻醉剂可以调节突触活动 因此可以想象，它们也可能会影响 脑缺血的病理生理学和结果。近期数据 研究表明，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的病理生理学中起重要作用 受伤。这里将评估的假设是确定的 麻醉剂通过减少缺血性脑损伤来减轻缺血性脑损伤 兴奋性毒性。第一个努力将是确定 麻醉剂的保护作用，与其对人的影响无关 局灶性脑缺血大鼠模型中的体温调节。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。首先是判断是否 麻醉剂通过减少谷氨酸的释放来减少兴奋性毒性 局灶性缺血期间。下一阶段是确定是否 麻醉剂可减少直接输注到体内所造成的损伤 大脑中存在特异性谷氨酸受体激动剂 NMDA 和 AMPA。在 第三阶段，麻醉剂对皮质扩散性抑制的影响 （CSD）将被确定。