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
- 来源:
- 关键词:AblationAdultAnimal ModelAnti-Inflammatory AgentsAntibodiesAreaAtherosclerosisAutomobile DrivingBiochemistryBlood VesselsBone MarrowBrainBrain regionCD36 geneCell membraneCell physiologyCellsCerebrovascular DisordersCholesterolChronicCicatrixCognitionDataDementiaDoseEncephalomalaciaEnzymesExcisionFDA approvedFemaleFoam CellsFoundationsGoalsHeartHematogenousHippocampusHumanImmuneImpaired cognitionIndividualInfarctionInfiltrationInflammasomeInflammationInflammatoryInflammatory ResponseInjuryIschemiaKnowledgeLipidsLiver X ReceptorMacrophageMediatingMicrogliaModelingMolecularMouse StrainsMusMyelinMyelogenousMyeloid CellsMyocardial InfarctionNerve DegenerationOutcomePathway interactionsPersonsPhagocytesPlasmaProcessProductionPublishingQuality of lifeRecommendationRecoveryResearchRoleSignal TransductionStrokeSurvivorsTestingTherapeuticTherapeutic EffectTimeTissuesTransplantationUp-Regulationagedbehavior measurementbrain tissuechronic strokecognitive functioncytokineexperiencehealinghydroxypropyl-beta-cyclodextrinimprovedlipid metabolismlipidomicsmalemouse modelneurotoxicnoveloxidized low density lipoproteinpost strokepost stroke cognitive impairmentpost stroke dementiapreventprotein expressionsensorsexsingle-cell RNA sequencingsolutestroke modelstroke recoverytranscriptional reprogrammingvascular cognitive impairment and dementia
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)
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
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)
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
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
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
- 批准号:
10065645 - 财政年份:2023
- 资助金额:
$ 201.69万 - 项目类别:
Collaborative R&D
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)