Reciprocal brain-lung responses in post-stroke pneumonia

中风后肺炎的脑肺交互反应

• 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
• 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

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。