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：
Charles S Dela Cruz
金额：
$ 25.13万
依托单位：
YALE UNIVERSITY
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：
https://reporter.nih.gov/project-details/10754060
关键词：
Affect Aging Alveolar Anti-Bacterial Agents Antibiotics Apoptosis Aspiration Pneumonia Bacterial Infections Blood capillaries Body Weight Brain Brain Injuries Bronchoalveolar Lavage Fluid CXCL1 gene Cause of Death Cells Cerebral Ischemia Clinical Trials Cognitive Complication Critical Care Data Endothelial Cells Event Experimental Models Feasibility Studies Female Flow Cytometry Foundations Gene Expression Profiling Genetic Transcription Goals Growth Host Defense Immune response Immunity Immunofluorescence Immunologic Immunologist Immunosuppression Impairment In Vitro Incidence Infection Inflammatory Inflammatory Response Interferon Receptor Interferon Type I Interferons Interleukin-6 Investigation Ischemic Stroke Klebsiella Infections Klebsiella pneumoniae Knock-out Lung Lung infections Microglia Middle Cerebral Artery Occlusion Modeling Morbidity - disease rate Mus Natural Immunity Neuroimmune Neuroimmunomodulation Neurological outcome Neurologist Neutrophil Activation Neutrophil Infiltration Organ Outcome Pathogenicity Patients Peripheral Physicians Pneumonia Predisposition Production Prognosis Recovery Recovery of Function Regimen Reperfusion Therapy Research Personnel Resolution Respiratory Tract Infections Risk Role Signal Transduction Spleen Stains Stroke Structure of parenchyma of lung Supportive care T-Lymphocyte Testing Time United States Up-Regulation Weight Gain Work antimicrobial behavioral outcome brain endothelial cell chemokine cost cytokine disability experimental study extracellular functional disability immunoregulation improved improved outcome in vivo male migration monocyte mortality neurobehavioral neuroinflammation neurological recovery neutrophil post stroke prevent prophylactic response single-cell RNA sequencing stroke outcome stroke patient stroke recovery targeted treatment therapeutic 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.

项目摘要中风是美国残疾的主要原因。中风患者的风险增加严重的肺炎和中风后肺炎与较差的结局有关。这个多PI项目将利用中风神经科医生/免疫学家和肺重症监护的互补专业知识医师/免疫学家共同解决中风中严重肺炎风险增加的机制患者和中风后神经炎症和神经系统恢复的失调机制。在我们的缺血性中风和肺炎克雷伯氏菌的实验模型中的初步工作证明了这一点细菌接种到肺部导致嗜中性粒细胞募集减少并增加细菌中风后传播。此外，肺炎会导致神经炎症增强并增加中风后小胶质细胞和内皮细胞中的干扰素反应。主要假设是中风导致中性粒细胞功能受损，使细菌逃生并通过体内传播这反过来导致了大脑神经炎症和进一步脑损伤的延迟。这该提案的总体目标是确定新的治疗靶标，以减少中风后肺炎并改善。中风后的结果。