Isolation and characterization of neural stem/progenitor cells from post-stroke cerebral cortex in mice

The CNS has the potential to marshal strong reparative mechanisms, including activation of endogenous neurogenesis, after a brain injury such as stroke. However, the response of neural stem/progenitor cells to stroke is poorly understood. Recently, neural stem/progenitor cells have been identified in the cerebral cortex, as well as previously recognized regions such as the subventricular or subgranular zones of the hippocampus, suggesting that a contribution of cortex‐derived neural stem/progenitor cells may repair ischemic lesions of the cerebral cortex. In the present study, using a highly reproducible murine model of cortical infarction, we have found nestin‐positive cells in the post‐stroke cerebral cortex, but not in the non‐ischemic cortex. Cells obtained from the ischemic core of the post‐stroke cerebral cortex formed neurosphere‐like cell clusters expressing nestin; such cells had the capacity for self‐renewal and differentiated into electrophysiologically functional neurons, astrocytes and myelin‐producing oligodendrocytes. Nestin‐positive cells from the stroke‐affected cortex migrated into the peri‐infarct area and differentiated into glial cells in vivo. Although we could not detect differentiation of nestin‐positive cells into neurons in vivo, our current observations indicate that endogenous neural stem/progenitors with the potential to become neurons can develop within post‐stroke cerebral cortex.