Despite intense research, interventions that improve outcome following ischemic stroke remain elusive. Immunosuppression is an increasingly well recognized consequence of acute injury to the central nervous system (CNS), and infection is a leading cause of secondary complication, prolonged ICU stays and increased mortality in patients with stroke. Although associations between immune function and clinical outcome in stroke have been debated, identification and pre-clinical targeting of potential mechanisms of stroke-induced immunosuppression remain critical areas of study. The most commonly reported immunological deficits associated with ischemic stroke are seen within the cellular immune compartment, which include lymphopenia and decreased T cell function. Critically, these abnormalities mirror those seen in patients with malignant brain tumors, in whom we recently a novel axis of immunosuppression involving the release of the enzyme Arginase 1 (ARG1) from activated neutrophils. In collaboration with Dr. Allen Waziri in Neurosurgery, we are testing the hypothesis that a similar mechanism exists in the setting of ischemic stroke, and we propose that targeting this upstream mediator of T-cell inhibition may improve immune function in affected patients.