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).
项目摘要 数十年的研究表明,包括中风在内的脑血管疾病与 随后的认知障碍和痴呆。然而,血管对认知障碍的贡献, 痴呆症(VCID)仍不清楚。我们已经证明中风后有慢性炎症反应 在动物模型中,它会加重中风后的损伤,导致延迟的认知障碍。因此, 对中风的慢性炎症反应是潜在的VCID。我们最近证明,在分子水平上, 水平,中风的慢性炎症反应与动脉粥样硬化非常相似, 存在泡沫细胞、胆固醇结晶,以及特异性细胞因子和降解性细胞因子的非常相似的表达。 内切酶在这方面,已知髓样细胞内过度的脂质加工是骨髓细胞增殖的驱动因素。 动脉粥样硬化,其特征是巨噬细胞内脂质代谢失调和高脂血症的产生。 神经毒性细胞因子和降解酶的浓度。脂质是主要的结构成分, 髓磷脂,因此是人脑的主要成分。因此,我们的总体假设是 中风后,浸润的巨噬细胞和驻留的小胶质细胞会被巨大的体积所压倒 胆固醇和其他脂质来源于髓鞘和其他细胞膜的分解,因此, 引起上述慢性炎症反应。我们认为细胞因子的渗透和 在梗塞内产生的降解酶进入邻近的脑区域是脑梗塞的主要原因。 脑软化,或“软化”,发生在慢性中风梗塞周围的组织。因此,在本发明中, 帮助吞噬细胞处理大量脂质碎片的治疗方法, 脑组织可以缓和对中风的慢性炎症反应并保护周围的脑组织, 从而促进大脑更健康的愈合并改善恢复。在梗塞部位 在对认知重要的大脑区域内或附近,这种治疗甚至可以预防痴呆症。 因此,本提案的目标是确定产生的促炎脂质种类和途径 触发,由脑卒中后大脑脂质成分的分解(目标1);定义个体 促炎脂质传感器在驱动中风慢性炎症反应中的作用(目标2);以及 优化我们在慢性炎症区域内的脂质清除方法,以改善恢复并预防 迟发性认知障碍(Aim 3)。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Kristian Paul Doyle其他文献

Kristian Paul Doyle的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ 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:

相似海外基金

Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
  • 批准号:
    MR/Z503605/1
  • 财政年份:
    2024
  • 资助金额:
    $ 201.69万
  • 项目类别:
    Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
  • 批准号:
    2336167
  • 财政年份:
    2024
  • 资助金额:
    $ 201.69万
  • 项目类别:
    Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
  • 批准号:
    2402691
  • 财政年份:
    2024
  • 资助金额:
    $ 201.69万
  • 项目类别:
    Standard Grant
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
  • 批准号:
    2341428
  • 财政年份:
    2024
  • 资助金额:
    $ 201.69万
  • 项目类别:
    Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
  • 批准号:
    24K12150
  • 财政年份:
    2024
  • 资助金额:
    $ 201.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
  • 批准号:
    DE240100561
  • 财政年份:
    2024
  • 资助金额:
    $ 201.69万
  • 项目类别:
    Discovery Early Career Researcher Award
RUI: Evaluation of Neurotrophic-Like properties of Spaetzle-Toll Signaling in the Developing and Adult Cricket CNS
RUI:评估发育中和成年蟋蟀中枢神经系统中 Spaetzle-Toll 信号传导的神经营养样特性
  • 批准号:
    2230829
  • 财政年份:
    2023
  • 资助金额:
    $ 201.69万
  • 项目类别:
    Standard Grant
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 201.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
  • 批准号:
    23K07552
  • 财政年份:
    2023
  • 资助金额:
    $ 201.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
  • 批准号:
    23K07559
  • 财政年份:
    2023
  • 资助金额:
    $ 201.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了