Stroke is a leading cause of disability in the United States, yet it has limited treatment options. Stem cell therapy offers a novel therapeutic strategy for stroke, and several clinical trials are underway. We are investigating the mechanisms by which stem cells enhance recovery in preclinical animal models of stroke. In the first year of this award we have found that after transplanting our stem cells into the stroke brain they only survive for a short time, and die before their effect on behavior recovery is observable. This implies that the transplanted cells act by triggering a cascade of events while they are present, which eventually leads to recovery. We are investigating what these ‘trigger’ events are. To this end we have made significant progress in developing sensitive tests to measure the effects of the transplanted cells on brain activity, plasticity, and inflammation. We are making on-track progress investigating how the stem cell-induced changes in these parameters relate to cell-induced functional recovery.