Integrated Systems Neuroscience Studies of Anaesthesia

麻醉的综合系统神经科学研究

• 批准号: 9209574
• 负责人: EMERY N BROWN
• 金额: $ 179.19万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-10 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9209574
• 关键词: Absence of pain sensation; Address; Adrenergic Agonists; Adverse effects; Amnesia; Anesthesia procedures; Anesthetics; Arousal; Behavioral; Brain; Caregivers; Coma; Data Analyses; Dexmedetomidine; Disease; Drug Delivery Systems; Drug effect disorder; Electroencephalography; General Anesthesia; Hallucinations; Human; Ketamine; Knowledge; Lead; Mental Depression; Modeling; Molecular Target; Monitor; NMDA receptor antagonist; Nausea and Vomiting; Neurosciences; Operative Surgical Procedures; Pain; Patients; Performance; Pharmaceutical Preparations; Physiological; Propofol; Research; Rodent Model; Sedation procedure; Sleep; Statistical Methods; Study models; System; Time; Translating; Unconscious State; United States; base; cognitive system; experimental study; fascinate; improved; insight; man; mathematical model; mind control; molecular site; neural circuit; neurophysiology; neurotoxicity; nonhuman primate; novel strategies; post-operative cognitive dysfunction; programs; relating to nervous system; sevoflurane

OVERALL ABSTRACT General anesthesia is a fascinating man-made, neurophysiological phenomenon that has been developed empirically over many years to enable safe and humane performance of surgical and non-surgical procedures. Specifically it is a drug-induced condition consisting of unconsciousness, amnesia, analgesia and immobility, along with physiological stability. General anesthesia is administered daily to 60,000 patients in the United States, the mechanisms for how anesthetics act in the brain to create the states of anesthesia are not well understood. Significant progress has been made recently in characterizing the molecular sites that anesthetics target. However, how actions at specific molecular targets lead to the behavioral states is less well understood. Addressing this issue requires a systems neuroscience approach to define how actions of the drugs at specific molecular targets and neural circuits lead to a behavioral state of general anesthesia. In this program project entitled, Integrated Systems Neuroscience Studies of Anesthesia, we will develop an integrated systems neuroscience program consisting of human, non-human primate, rodent and modeling studies of four anesthetics: the GABAA agents, propofol and sevoflurane; the alpha-2 adrenergic agonist, dexmedetomidine; and the NMDA receptor antagonist, ketamine. The program project will also include a DATA ANALYSIS CORE, which will provide assistance with data analysis and conduct research on statistical methods. The Specific Aims are to understand how the actions of the anesthetics at specific molecular targets and neural circuits produce the oscillatory dynamics (EEG rhythms, changes in LFPs and neural spiking activity) that are likely a primary common mechanism through which anesthetics create altered states of arousal (sedation, hallucination, unconsciousness). The research will develop new, fundamental knowledge about the neurophysiological mechanisms of anesthetic actions that will have broad impact. This new knowledge will offer a new approach to real-time monitoring and control of brain states of patients receiving general anesthesia and sedation. Anesthesia caregivers will be able to relate the prominent oscillatory dynamics induced by anesthetics to their altered states of arousal through their actions at specific molecular targets and in specific neural circuits. Improved neurophysiologically-based monitoring and drug delivery strategies offer the promise of reducing the undesirable anesthetic side effects such as nausea, vomiting, neurotoxicity and post-operative cognitive dysfunction. This research will provide new, fundamental quantitative insights into the workings of the brain's arousal and cognitive systems that may translate into new approaches to creating the states of general anesthesia along with ways to treat disorders of arousal such as sleep, depression, coma and pain.

总体抽象 全身麻醉是一种引人入胜的人造神经生理现象，已经开发 从经验上讲，多年来，可以实现手术和非手术程序的安全和人道的表现。 具体而言，它是一种药物引起的疾病，包括无意识，健忘症，镇痛和不动， 以及生理稳定性。每天对联合的60,000名患者进行全身麻醉 国家，麻醉药在大脑中如何创建麻醉状态的机制不好 理解。最近在表征麻醉的分子位点方面取得了重大进展 目标。但是，特定分子靶标的行动如何导致行为状态的理解较少。 解决此问题需要采用系统神经科学方法来定义药物在特定方面的作用 分子靶标和神经回路导致全身麻醉的行为状态。在这个程序项目中 我们将开发一个集成系统的题为“综合系统神经科学研究” 神经科学计划由人类，非人类灵长类动物，啮齿动物和建模研究组成 麻醉药：Gabaa特工，丙泊酚和七氟烷； Alpha-2肾上腺素激动剂，右美托咪定； NMDA受体拮抗剂氯胺酮。程序项目还将包括数据分析核心， 这将为数据分析提供帮助，并对统计方法进行研究。具体 目的是了解麻醉剂在特定分子靶标和神经回路上的作用 产生振荡动力学（EEG节奏，LFP的变化和神经尖峰活动）可能是 麻醉剂会产生改变的唤醒状态的主要常见机制（镇静， 幻觉，无意识）。该研究将发展有关 麻醉作用的神经生理机制将产生广泛的影响。这个新知识将 提供一种新的方法来实时监测和控制接受一般患者的大脑状态 麻醉和镇静。麻醉护理人员将能够联系出突出的振荡动力学 麻醉剂通过在特定分子靶标和 在特定的神经回路中。改进的基于神经生理学的监测和药物输送策略提供 减少不良麻醉副作用的希望，例如恶心，呕吐，神经毒性和 术后认知功能障碍。这项研究将为您提供新的，基本的定量见解 大脑唤醒和认知系统的工作，这些系统可能转化为创建新方法 全身麻醉状态以及治疗唤醒疾病的方法，例如睡眠，抑郁，昏迷和 疼痛。