Active Induction of Emergence from General Anesthesia

描述（由申请人提供）：培训计划：本提案描述了一项为期5年的指导性研究培训计划，旨在培养麻醉机制方面的独立研究者。主要研究者是哈佛医学院（HMS）的麻醉助理教授和马萨诸塞州总医院（MGH）的麻醉师，具有麻醉药理学和电生理学背景。他的导师，埃默里·N博士。布朗，是沃伦M。Zapol HMS麻醉学教授，系内计算神经科学教授。他是马萨诸塞州理工学院（MIT）的脑与认知科学教授，以及HMS和MIT的健康科学与技术教授。通过指导临床科学家研究职业发展奖，主要研究者将获得系统神经科学的新知识和技能，足以开发独立的研究计划。他将在系里学习课程。他的研究培训将在麻省理工学院麻省总医院和加州大学圣地亚哥分校的实验室进行。本提案的长期目标是为主要研究者准备一个成功的独立职业生涯，使用系统神经科学方法研究麻醉机制。 研究计划：越来越多的证据表明，大脑中的上升唤醒通路促进了全身麻醉（GA）的出现。阐明这些机制可能会导致麻醉患者的唤醒状态，更好的治疗苏醒谵妄，更好的神经生理监测器，以检测术中意识，并最终更安全，更有效的麻醉实践的药理学控制。我们的初步数据表明，在稳态暴露于异氟烷期间，多巴胺能和胆碱能唤醒回路的药理学激活产生不同的唤醒状态，其特征在于不同的行为和神经生理学终点。本项目的目的是阐明多巴胺能和胆碱能唤醒回路在促进GA出现中的作用。使用药理学和脑微刺激技术相结合，我们将探讨行为和神经生理相关的积极诱导出现GA。 公共卫生相关性：许多与全身麻醉（GA）苏醒相关的临床问题尚未得到解决，因为苏醒背后的神经机制尚未阐明。本项目的目的是阐明多巴胺能和胆碱能唤醒回路在促进GA出现中的作用。这些机制的知识可能会导致临床护理的进步，包括控制患者觉醒状态的新方法，更好地治疗出现谵妄，以及改善神经生理监测器，优化麻醉剂量并保护患者免受术中意识。

DESCRIPTION (provided by applicant): Training Plan: This proposal describes a mentored 5-year research training program for the development of an independent investigator in anesthetic mechanisms. The Principal Investigator is an Assistant Professor of Anaesthesia at Harvard Medical School (HMS) and a faculty anesthesiologist at Massachusetts General Hospital (MGH), with a background in anesthetic pharmacology and electrophysiology. His mentor, Dr. Emery N. Brown, is Warren M. Zapol Professor of Anaesthesia at HMS, Professor of Computational Neuroscience in the Dept. of Brain and Cognitive Sciences at the Massachusetts Institute of Technology (MIT), and Professor of Health Sciences and Technology at HMS and MIT. With the Mentored Clinical Scientist Research Career Development Award, the Principal Investigator will acquire new knowledge and skills in systems neuroscience sufficient to develop an independent research program. He will take courses in the Dept. of Brain and Cognitive Sciences at MIT, and his research training will take place in laboratories at MGH, MIT, and the University of California, San Diego. The long-term objective of this proposal is to prepare the Principal Investigator for a successful independent career studying anesthetic mechanisms using a systems neuroscience approach. Research Plan: Accumulating evidence suggests that ascending arousal pathways in the brain promote emergence from general anesthesia (GA). Elucidating these mechanisms may lead to improved pharmacological control over the arousal states of anesthetized patients, better treatments for emergence delirium, better neurophysiological monitors to detect intraoperative awareness, and ultimately a safer and more efficient practice of anesthesiology. Our preliminary data suggest that pharmacological activation of dopaminergic and cholinergic arousal circuits during steady-state exposure to isoflurane produce distinct arousal states that are characterized by different behavioral and neurophysiological endpoints. The goal of this project is to elucidate the roles of dopaminergic and cholinergic arousal circuits in promoting emergence from GA. Using a combination of pharmacological and brain microstimulation techniques, we will probe the behavioral and neurophysiological correlates of actively induced emergence from GA. PUBLIC HEALTH RELEVANCE: Many of the clinical problems related to emergence from general anesthesia (GA) have not been solved because the neural mechanisms underlying emergence have not been elucidated. The goal of this project is to elucidate the roles of dopaminergic and cholinergic arousal circuits in promoting emergence from GA. Knowledge of these mechanisms may lead to advances in clinical care including novel methods to control the arousal states of patients, better treatments for emergence delirium, and improved neurophysiological monitors that optimize anesthetic dosing and protect patients from intraoperative awareness.