The role of astrocytes in emergence from volatile anesthetics

星形胶质细胞在挥发性麻醉剂苏醒中的作用

基本信息

  • 批准号:
    10340339
  • 负责人:
  • 金额:
    $ 42.33万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-03-01 至 2023-02-28
  • 项目状态:
    已结题

项目摘要

Project Summary Our overarching goal is to define the molecular and cellular mechanisms underlying the actions of volatile anesthetics (VAs). Our objective in the studies proposed here, which represent the next step in pursuing this goal, is to mechanistically define the functions of astrocytes that underly their involvement in the process of emergence from anesthesia with VAs. We hypothesize, based on substantial recent and preliminary data, astrocyte mitochondrial electron transport chain (ETC) function supports normal emergence through maintenance of astrocyte calcium signaling, gliotransmitter release, and metabolic support to neurons. We further hypothesize that specific, spatially defined, populations of astrocytes within the central nervous system (CNS) drive emergence through their local support of neuronal synapses involved in emergence. Our experiments will take advantage of pure primary astrocyte cell culture, a mouse model for cell-specific disruption of mitochondrial function through cre-mediated excision of the ETC complex I protein Ndufs4, and stereotactic microinjection targeted viral delivery of an astrocyte promoter driven cre-recombinase to enable brain region-specific disruption of Ndufs4 specifically in astrocytes. These models will allow us to characterize the astrocyte functions impacted by VAs and the population of astrocytes involved in emergence. Specifically, they will allow us to: i) define the effects of VAs on astrocyte calcium signaling and mitochondrial function, and the mechanistic links between the two, in vitro; ii) characterize the effects of VAs on astrocyte gliotransmitter release; iii) characterize the impact of VAs on astrocyte metabolites which support neuronal function; iv) define the astrocyte population, defined by region, responsible for supporting emergence from anesthesia with VAs. Ultimately, this work will greatly advance our understanding of the mechanisms of VA activity and the process of emergence. Relevance Despite their prevalence, the precise targets of VAs, and the mechanisms underlying their pleiotropic effects, are largely undefined. Emergence is a daily occurrence for thousands of patients, but the process of emergence is poorly understood. Delays in emergence are associated with anxiety, confusion, resistive activity, delays in the operating room, increased risks of injury, and significant medical costs. If the mechanisms of emergence can be resolved, it may be possible to develop strategies for active promotion of recovery of consciousness.
项目总结

项目成果

期刊论文数量(0)
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会议论文数量(0)
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Simon C Johnson其他文献

Evaluating the efficacy of vatiquinone in preclinical models of mitochondrial disease
评估万替醌在线粒体疾病临床前模型中的功效
  • DOI:
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Ernst;Yihan Chen;Michael Mulholland;Vivian Truong;K. James;Allison Hanaford;Simon C Johnson
  • 通讯作者:
    Simon C Johnson

Simon C Johnson的其他文献

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{{ truncateString('Simon C Johnson', 18)}}的其他基金

The role of astrocytes in emergence from volatile anesthetics
星形胶质细胞在挥发性麻醉剂苏醒中的作用
  • 批准号:
    10776191
  • 财政年份:
    2022
  • 资助金额:
    $ 42.33万
  • 项目类别:
Developmental mechanisms of CNS pathology in mitochondrial disease
线粒体疾病中枢神经系统病理学的发育机制
  • 批准号:
    10296147
  • 财政年份:
    2021
  • 资助金额:
    $ 42.33万
  • 项目类别:
Developmental mechanisms of CNS pathology in mitochondrial disease
线粒体疾病中枢神经系统病理学的发育机制
  • 批准号:
    10468301
  • 财政年份:
    2021
  • 资助金额:
    $ 42.33万
  • 项目类别:
The role of ketone metabolism in sequelae resulting from volatile anesthetic exposure.
酮代谢在挥发性麻醉剂暴露引起的后遗症中的作用。
  • 批准号:
    10425335
  • 财政年份:
    2019
  • 资助金额:
    $ 42.33万
  • 项目类别:
The role of ketone metabolism in sequelae resulting from volatile anesthetic exposure.
酮代谢在挥发性麻醉剂暴露引起的后遗症中的作用。
  • 批准号:
    10187595
  • 财政年份:
    2019
  • 资助金额:
    $ 42.33万
  • 项目类别:
The role of mTOR in mitochondrial encephalopathy
mTOR 在线粒体脑病中的作用
  • 批准号:
    9920237
  • 财政年份:
    2017
  • 资助金额:
    $ 42.33万
  • 项目类别:
Functional Characterization and Physiological Consequences of Human Longevity-Associated IGF1R Variants
人类长寿相关 IGF1R 变异体的功能特征和生理后果
  • 批准号:
    9136482
  • 财政年份:
    2015
  • 资助金额:
    $ 42.33万
  • 项目类别:
Functional Characterization and Physiological Consequences of Human Longevity-Associated IGF1R Variants
人类长寿相关 IGF1R 变异体的功能特征和生理后果
  • 批准号:
    9062284
  • 财政年份:
    2015
  • 资助金额:
    $ 42.33万
  • 项目类别:

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