Reciprocal brain-lung responses in post-stroke pneumonia

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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.