Reciprocal brain-lung responses in post-stroke pneumonia

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， 严重肺炎和中风后肺炎与不良结局相关。这个多PI项目将 利用中风神经学家/免疫学家和肺部重症监护的互补专业知识 医生/免疫学家共同解决中风中严重肺炎风险增加的机制 卒中后神经炎症失调和神经功能恢复的机制。 我们在缺血性中风和克雷伯氏肺炎实验模型中的初步工作表明， 细菌接种到肺中导致中性粒细胞募集减少和细菌增加。 中风后的传播此外，肺炎导致神经炎症增强， 脑卒中后小胶质细胞和内皮细胞的干扰素反应主要假设是中风 导致中性粒细胞功能受损，从而允许细菌逃逸并通过身体传播， 这又导致脑中神经炎症消退的延迟和进一步的脑损伤。的 该提案的总体目标是确定新的治疗目标，以减少卒中后肺炎， 中风后的结果

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.