My overarching hypothesis is that the immune system – driven by an autoreactivity to CNS-derived antigens – plays a fundamental role in neuronal plasticity within the CNS. B cells, T cells, and natural killer (NK) T cells comprise the adaptive component of the immune system, with their interactions initiated by antigen recognition. In stroke, I hypothesize that long-term plasticity requires autoreactive T and B cell responses within the parenchyma, derived from lymphocyte populations sensitized to CNS antigens in the periphery. My preliminary data show that CD4 and CD8 T cells, as well as B cells, respond to specific immunogenic peptide sequences from neuronally-derived proteins that could potentially facilitate such processes as dendritic pruning, synaptogenesis, and axonal outgrowth in the ischemic brain. Although I use preclinical studies to investigate the mechanisms by which autoimmune responses affect post-stroke plasticity (e.g., protection from excitotoxicity, dendritic pruning), it is critical to concomitantly confirm and characterize these cells in humans. My clinical studies into the role of neuroinflammation during brain injury and repair has expanded beyond the field of ischemic stroke to also include subjects with amnestic mild cognitive impairment and pediatric patients on ventilator and hemodynamic support who experience stroke. The combination of preclinical and clinical studies reflects both my own training, which included a clinical postdoctoral fellowship, and my ongoing scientific philosophy that translational research will hasten the collective understanding of functional recovery during and following brain injury.