Reciprocal brain-lung responses in post-stroke pneumonia
中风后肺炎的脑肺交互反应
基本信息
- 批准号:10754060
- 负责人:
- 金额:$ 25.13万
- 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:2023-08-01 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAgingAlveolarAnti-Bacterial AgentsAntibioticsApoptosisAspiration PneumoniaBacterial InfectionsBlood capillariesBody WeightBrainBrain InjuriesBronchoalveolar Lavage FluidCXCL1 geneCause of DeathCellsCerebral IschemiaClinical TrialsCognitiveComplicationCritical CareDataEndothelial CellsEventExperimental ModelsFeasibility StudiesFemaleFlow CytometryFoundationsGene Expression ProfilingGenetic TranscriptionGoalsGrowthHost DefenseImmune responseImmunityImmunofluorescence ImmunologicImmunologistImmunosuppressionImpairmentIn VitroIncidenceInfectionInflammatoryInflammatory ResponseInterferon ReceptorInterferon Type IInterferonsInterleukin-6InvestigationIschemic StrokeKlebsiella InfectionsKlebsiella pneumoniaeKnock-outLungLung infectionsMicrogliaMiddle Cerebral Artery OcclusionModelingMorbidity - disease rateMusNatural ImmunityNeuroimmuneNeuroimmunomodulationNeurological outcomeNeurologistNeutrophil ActivationNeutrophil InfiltrationOrganOutcomePathogenicityPatientsPeripheralPhysiciansPneumoniaPredispositionProductionPrognosisRecoveryRecovery of FunctionRegimenReperfusion TherapyResearch PersonnelResolutionRespiratory Tract InfectionsRiskRoleSignal TransductionSpleenStainsStrokeStructure of parenchyma of lungSupportive careT-LymphocyteTestingTimeUnited StatesUp-RegulationWeight GainWorkantimicrobialbehavioral outcomebrain endothelial cellchemokinecostcytokinedisabilityexperimental studyextracellularfunctional disabilityimmunoregulationimprovedimproved outcomein vivomalemigrationmonocytemortalityneurobehavioralneuroinflammationneurological recoveryneutrophilpost strokepreventprophylacticresponsesingle-cell RNA sequencingstroke outcomestroke patientstroke recoverytargeted treatmenttherapeutic target
项目摘要
Project Summary
Stroke is the leading cause of disability in the United States. Patients with stroke are at increased risk of
severe pneumonia and post-stroke pneumonia is associated with poor outcomes. This multi-PI project will
leverage the complementary expertise of a Stroke Neurologist/Immunologist and a Pulmonary Critical Care
physician/Immunologist to jointly tackle the mechanisms of increased risk of severe pneumonia in stroke
patients and the mechanisms of dysregulated neuroinflammation and neurological recovery after stroke.
Preliminary work in our experimental model of ischemic stroke and Klebsiella pneumonia demonstrates that
bacterial inoculation into the lungs leads to reduced neutrophil recruitment and increased bacterial
dissemination after stroke. Furthermore, pneumonia leads to enhanced neuroinflammation and increased
interferon responses in the microglia and endothelial cells after stroke. The primary hypothesis is that stroke
leads to an impairment in neutrophil function allowing for bacterial escape and dissemination through the body,
which in turn leads to a delay in the resolution of neuroinflammation in the brain and further brain injury. The
overall goal of the proposal is to identify new treatment targets to reduce post-stroke pneumonia and improve
outcomes after stroke.
项目摘要
在美国,中风是导致残疾的主要原因。中风患者患中风的风险增加
重症肺炎和中风后肺炎与预后不良有关。这个多PI项目将
利用卒中神经学家/免疫学家和肺部重症监护专家的互补专业知识
内科医生/免疫学家共同解决中风患者严重肺炎风险增加的机制
患者与卒中后神经炎症和神经恢复失调的机制。
在我们的缺血性中风和肺炎克雷伯菌实验模型中的初步工作表明
肺部接种细菌可减少中性粒细胞募集,增加细菌数量
中风后的扩散。此外,肺炎会导致神经炎症加剧,并增加
卒中后小胶质细胞和血管内皮细胞的干扰素反应。主要的假设是中风
导致中性粒细胞功能受损,导致细菌逃逸并在体内传播,
这反过来又会导致大脑中神经炎症的消退延迟,并进一步造成脑损伤。这个
该提案的总体目标是确定新的治疗目标,以减少中风后肺炎并改善
中风后的转归。
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)
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Charles S Dela Cruz其他文献
Charles S Dela Cruz的其他文献
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{{ truncateString('Charles S Dela Cruz', 18)}}的其他基金
Viral and immune-mediated CNS pathology during SARS-CoV-2 infection
SARS-CoV-2 感染期间病毒和免疫介导的中枢神经系统病理学
- 批准号:
10554829 - 财政年份:2020
- 资助金额:
$ 25.13万 - 项目类别:
MAVS-Mediated Pulmonary Inflammation and Injury Response During Cigarette Smoke Exposure and Influenza Viral Infection and in COPD
香烟烟雾暴露和流感病毒感染以及 COPD 期间 MAVS 介导的肺部炎症和损伤反应
- 批准号:
9780742 - 财政年份:2019
- 资助金额:
$ 25.13万 - 项目类别:
MAVS-Mediated Pulmonary Inflammation and Injury Response During Cigarette Smoke Exposure and Influenza Viral Infection and in COPD
香烟烟雾暴露和流感病毒感染以及 COPD 期间 MAVS 介导的肺部炎症和损伤反应
- 批准号:
10292925 - 财政年份:2019
- 资助金额:
$ 25.13万 - 项目类别:
MAVS-Mediated Pulmonary Inflammation and Injury Response During Cigarette Smoke Exposure and Influenza Viral Infection and in COPD
香烟烟雾暴露和流感病毒感染以及 COPD 期间 MAVS 介导的肺部炎症和损伤反应
- 批准号:
10045508 - 财政年份:2019
- 资助金额:
$ 25.13万 - 项目类别:
MAVS-Mediated Pulmonary Inflammation and Injury Response During Cigarette Smoke Exposure and Influenza Viral Infection and in COPD
香烟烟雾暴露和流感病毒感染以及 COPD 期间 MAVS 介导的肺部炎症和损伤反应
- 批准号:
10515290 - 财政年份:2019
- 资助金额:
$ 25.13万 - 项目类别:
Molecular and Cellular Interactions Between Cigarette Smoke Exposure and RSV
香烟烟雾暴露与 RSV 之间的分子和细胞相互作用
- 批准号:
7953132 - 财政年份:2010
- 资助金额:
$ 25.13万 - 项目类别:
Molecular and Cellular Interactions Between Cigarette Smoke Exposure and RSV
香烟烟雾暴露与 RSV 之间的分子和细胞相互作用
- 批准号:
8668779 - 财政年份:2010
- 资助金额:
$ 25.13万 - 项目类别:
Molecular and Cellular Interactions Between Cigarette Smoke Exposure and RSV
香烟烟雾暴露与 RSV 之间的分子和细胞相互作用
- 批准号:
8470223 - 财政年份:2010
- 资助金额:
$ 25.13万 - 项目类别:
Molecular and Cellular Interactions Between Cigarette Smoke Exposure and RSV
香烟烟雾暴露与 RSV 之间的分子和细胞相互作用
- 批准号:
8277248 - 财政年份:2010
- 资助金额:
$ 25.13万 - 项目类别:
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