? Stroke is the leading cause of adult disability due to the brain's limited functional recovery after ischemic injury. Stroke causes a localized process of cell death, but also induces neural stem cells to produce immature neurons which migrate to the site of injury and differentiate into mature neuronal phenotypes. This stem cell response generates new neurons at the site of stroke damage, suggesting a potential for neuronal regeneration after stroke. However, the molecular mechanisms of post-stroke neurogenesis and neuronal migration have not been well characterized. The experiments in this grant application will identify the developmental potential of adult CNS stem cells, use a novel experimental system to define the gene expression profile of migrating neuroblasts after stroke, and characterize the functional role of extracellular guidance cues in post-stroke neuronal migration. A better understanding of the molecular mechanisms of post-stroke neurogenesis and migration may lead to novel cell-replacement therapies that promote recovery and repair in the adult brain. ? ?
