Inflammation and delayed cognitive dysfunction after stroke

中风后炎症和迟发性认知功能障碍

基本信息

  • 批准号:
    10621096
  • 负责人:
  • 金额:
    $ 201.69万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-03-15 至 2026-02-28
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Decades of research have shown a strong association between cerebrovascular disease, including stroke, and subsequent cognitive impairment and dementia. However, vascular contributions to cognitive impairment and dementia (VCID) are still unclear. We have shown that there is a chronic inflammatory response following stroke that intensifies post-stroke injury, and in animal models, causes delayed cognitive impairment. As such, the chronic inflammatory response to stroke is a potential VCID. We recently demonstrated that at the molecular level, the chronic inflammatory response to stroke strongly resembles that seen in atherosclerosis due to the presence of foam cells, cholesterol crystals, and very similar expression of specific cytokines and degradative enzymes. In that regard, it is known that overwhelmed lipid processing within myeloid cells is a driver of atherosclerosis, features of which are dysregulated lipid metabolism within macrophages and production of high concentrations of neurotoxic cytokines and degradative enzymes. Lipids are principal structural components of myelin and are therefore major constituents of the human brain. Consequently, our overarching hypothesis is that following stroke, infiltrating macrophages and resident microglia become overwhelmed by the sheer volume of cholesterol and other lipids derived from the breakdown of myelin and other cell membranes and, as a result, cause the chronic inflammatory response described above. We propose that the permeation of cytokines and degradative enzymes produced within the infarct into neighboring brain regions is the principal cause of the encephalomalacia, or “softening,” that occurs to the tissue that surrounds chronic stroke infarcts. Thus, treatments that help phagocytic cells process the large amounts of lipid debris generated by the breakdown of brain tissue may temper the chronic inflammatory response to stroke and protect the surrounding brain tissue, thereby promoting healthier healing of the brain and improving recovery. In cases where the infarct is located within or adjacent to a brain region important for cognition, such treatments may even prevent dementia. Therefore, the goals of this proposal are to identify the pro-inflammatory lipid species generated, and pathways triggered, by the break-down of the lipid component of the brain following stroke (Aim 1); define the individual roles of pro-inflammatory lipid sensors in driving the chronic inflammatory response to stroke (Aim 2); and optimize our lipid removal approach within the area of chronic inflammation to improve recovery and prevent delayed cognitive impairment (Aim 3).
项目总结

项目成果

期刊论文数量(0)
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Kristian Paul Doyle其他文献

Kristian Paul Doyle的其他文献

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{{ truncateString('Kristian Paul Doyle', 18)}}的其他基金

Inflammation and delayed cognitive dysfunction after stroke
中风后炎症和迟发性认知功能障碍
  • 批准号:
    10626672
  • 财政年份:
    2022
  • 资助金额:
    $ 201.69万
  • 项目类别:
Interactions between the chronic sequelae of stroke and Alzheimer's disease
中风慢性后遗症与阿尔茨海默病之间的相互作用
  • 批准号:
    10621332
  • 财政年份:
    2019
  • 资助金额:
    $ 201.69万
  • 项目类别:
Interactions between the chronic sequelae of stroke and Alzheimer's disease
中风慢性后遗症与阿尔茨海默病之间的相互作用
  • 批准号:
    10418704
  • 财政年份:
    2019
  • 资助金额:
    $ 201.69万
  • 项目类别:
Interactions between the chronic sequelae of stroke and Alzheimer's disease
中风慢性后遗症与阿尔茨海默病之间的相互作用
  • 批准号:
    10202479
  • 财政年份:
    2019
  • 资助金额:
    $ 201.69万
  • 项目类别:
Cellular and molecular mechanisms of brain repair by glial scar formation following stroke
中风后神经胶质疤痕形成脑修复的细胞和分子机制
  • 批准号:
    9335461
  • 财政年份:
    2016
  • 资助金额:
    $ 201.69万
  • 项目类别:
Inflammation and delayed cognitive dysfunction after stroke
中风后炎症和迟发性认知功能障碍
  • 批准号:
    8779803
  • 财政年份:
    2014
  • 资助金额:
    $ 201.69万
  • 项目类别:
Inflammation and delayed cognitive dysfunction after stroke
中风后炎症和迟发性认知功能障碍
  • 批准号:
    8826622
  • 财政年份:
    2014
  • 资助金额:
    $ 201.69万
  • 项目类别:
Inflammation and delayed cognitive dysfunction after stroke
中风后炎症和迟发性认知功能障碍
  • 批准号:
    8279787
  • 财政年份:
    2012
  • 资助金额:
    $ 201.69万
  • 项目类别:
Inflammation and delayed cognitive dysfunction after stroke
中风后炎症和迟发性认知功能障碍
  • 批准号:
    8451271
  • 财政年份:
    2012
  • 资助金额:
    $ 201.69万
  • 项目类别:

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