Microglial mechanisms of postoperative CNS inflammation and cognitive decline

术后中枢神经系统炎症和认知能力下降的小胶质细胞机制

基本信息

  • 批准号:
    9010611
  • 负责人:
  • 金额:
    $ 49.97万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-09-15 至 2021-04-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): This project will investigate microglial involvement in cognitive impairment after surgery and general anesthesia. Cognitive impairment is prevalent and persistent in older surgical patients and associated with higher morbidity and cost. The cause is unknown but CNS inflammation is implicated. Microglia, the resident immune competent cells of the CNS, are major effectors of CNS inflammation, but until recently it was difficult to distinguish between resident microglia and myeloid cells that infiltrate the CNS durin stress because there were no known microglia specific genes encoding cell surface proteins. This is critical because resident microglia and infiltrating macrophages have separate and distinct immune functions. We propose a transcriptome / proteomincs / bioinformatics approach using a recently discovered unique molecular signature for microglia to investigate age-dependent microglia biology during and after surgery and anesthesia. Using such tools, we found there are fewer microglia in the old brain, that they express lower levels of immune-related and homeostatic genes, and that isoflurane anesthesia affects microglia in young vs. old mice differently. Based on these data, we propose microglial attrition and dysregulation in the old CNS are responsible for vulnerability to cognitive impairment after surgery and that surgery. Here we will identify the impact of surgery and general anesthesia on the molecular and functional signature of microglia; investigate the contribution of microglia to postoperative CNS inflammation and cognitive impairment using microglial ablation / replenishment; and rescue age-dependent cognitive vulnerability to surgery and anesthesia by immunomodulating microglia. Upon completion of the project, we will understand age differences in the molecular and functional properties of microglia, the role of resident microglia vs. infiltrating myeloid cels in surgery- induced CNS inflammation and cognitive decline, and how general anesthesia affects the process and defined a strategy for specifically targeting microglia to restore their homeostatic molecular signature, reduce CNS inflammation, and improve postoperative cognitive outcome in older subjects. Importantly, we will also specifically target microglia to restore their homeostatic molecular signature in order to reduce CNS inflammation and improve postoperative cognitive outcome. The work proposed is innovative because it uses state-of- the art methods and technology to explore a novel microglial mechanism for postoperative cognitive decline in older patients and significant because of the scale of the clinical problem and potential to identify new ways of preventing it.


项目成果

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会议论文数量(0)
专利数量(0)

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Oleg Butovsky其他文献

Oleg Butovsky的其他文献

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{{ truncateString('Oleg Butovsky', 18)}}的其他基金

Role of a novel risk loci HAVCR2 of late-onset Alzheimer's disease in the regulation of microglial response in neurodegeneration
迟发性阿尔茨海默病的新风险位点 HAVCR2 在调节神经退行性小胶质细胞反应中的作用
  • 批准号:
    10608400
  • 财政年份:
    2023
  • 资助金额:
    $ 49.97万
  • 项目类别:
Gender-dependent APOE4 regulation of neutrophil-microglia crosstalk in Alzheimer's disease
阿尔茨海默病中中性粒细胞-小胶质细胞串扰的性别依赖性 APOE4 调节
  • 批准号:
    10552667
  • 财政年份:
    2022
  • 资助金额:
    $ 49.97万
  • 项目类别:
Gender-dependent APOE4 regulation of neutrophil-microglia crosstalk in Alzheimer's disease
阿尔茨海默病中中性粒细胞-小胶质细胞串扰的性别依赖性 APOE4 调节
  • 批准号:
    10344242
  • 财政年份:
    2022
  • 资助金额:
    $ 49.97万
  • 项目类别:
APOE e4 negative regulation of microglia-astrocytes crosstalk in Alzheimer's disease
APOE e4 对阿尔茨海默病中小胶质细胞-星形胶质细胞串扰的负调节
  • 批准号:
    10429190
  • 财政年份:
    2022
  • 资助金额:
    $ 49.97万
  • 项目类别:
Xenon gas treatment to modulate microglia in neurodegenerative diseases
氙气治疗调节神经退行性疾病中的小胶质细胞
  • 批准号:
    10617078
  • 财政年份:
    2021
  • 资助金额:
    $ 49.97万
  • 项目类别:
Xenon gas treatment to modulate microglia in neurodegenerative diseases
氙气治疗调节神经退行性疾病中的小胶质细胞
  • 批准号:
    10259094
  • 财政年份:
    2021
  • 资助金额:
    $ 49.97万
  • 项目类别:
Targeting the miR-155 and APOE-TREM2 pathways to restore dysfunctional microglia in Alzheimer's disease
靶向 miR-155 和 APOE-TREM2 通路以恢复阿尔茨海默病中功能失调的小胶质细胞
  • 批准号:
    9926784
  • 财政年份:
    2017
  • 资助金额:
    $ 49.97万
  • 项目类别:
Role of Microglia in Retinitis Pigementosa
小胶质细胞在色素性视网膜炎中的作用
  • 批准号:
    9899490
  • 财政年份:
    2017
  • 资助金额:
    $ 49.97万
  • 项目类别:
Targeting the miR-155 and APOE-TREM2 pathways to restore dysfunctional microglia in Alzheimer’s disease
靶向 miR-155 和 APOE-TREM2 通路以恢复阿尔茨海默病中功能失调的小胶质细胞
  • 批准号:
    9219386
  • 财政年份:
    2017
  • 资助金额:
    $ 49.97万
  • 项目类别:
Restoration of homeostatic microglia in CNS inflammation
中枢神经系统炎症中小胶质细胞稳态的恢复
  • 批准号:
    10426253
  • 财政年份:
    2014
  • 资助金额:
    $ 49.97万
  • 项目类别:

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