Long-Term Stimulation of Neural Progenitor Cell Migration After Cortical Ischemia in Mice

Background and Purpose-Cortical ischemia induces neural progenitor cell migration toward the injury site; however, whether these cells are capable of maintaining the migratory response for a longer period after injury remains uncertain. Methods-We analyzed progenitor migration up to 1 year after induction of photothrombotic stroke to the mouse neocortex. Migrating progenitors identified as doublecortin positive cells (DCX+) were assessed using the immunohistochemistry and immunofluorescence. The thymidine analogues chlorodeoxyuridine and iododeoxyuridine were used to birth-date the progenitor cells. Results-In the striatum, we detected elevated numbers of DCX+ cells up to 6 weeks postlesion. In the corpus callosum and the peri-infarct cortex (Ctx), DCX+ cell numbers were increased up to 1 year. The orientation of the migrating progenitors was mostly aligned with the corpus callosum fiber tract at all time points; however, in the Ctx, they aligned parallel to the infarct border. The injured cortex continuously receives new progenitors up to 1 year after lesion. Cells born after lesion did not become mature neurons, although a portion of the migrating progenitors showed initial signs of differentiation into neurons. Conclusions-Neural progenitors might have a role in brain plasticity after cortical stroke, especially considering the prolonged window of migratory responses of up to 1 year after stroke lesion. (Stroke. 2011;42:3559-3565.)