Migration and fate of newly born cells after focal cortical ischemia in adult rats

Abstract

Neural cell migration and differentiation may participate in neural repair after adult brain injury; however, the survival and differentiation of newly born cells after different brain lesions are poorly understood. We have examined the migration and fate of bromodeoxyuridine (BrdU)-labeled cells after a highly reproducible focal ischemic lesion restricted to the frontoparietal cortex in adult rats. Thermocoagulation of pial blood vessels induces a circumscribed degeneration of all cortical layers while sparing the corpus callosum and striatum and increases cell proliferation in the subventricular zone (SVZ) and rostral migratory stream (RMS) within 7 days. We now show that, although the rostral migration of the newly born SVZ cells and their differentiation into neurons in the olfactory bulb were not affected by the lesion, numerous cells expressing the neuroblast marker doublecortin migrated laterally in the striatum and corpus callosum 5 days postinjury. In addition to the SVZ, BrdU-labeled cells were seen in the striatum, in the corpus callosum, and around the lesion. One month later, BrdU-labeled cells in the corpus callosum expressed transferrin and the pi isoform of glutathione-S-transferase (GST-pi), markers of oligodendrocytes. Other BrdU+ cells expressed a marker of astrocytes, but none expressed neuronal markers, suggesting that new neurons do not form or survive under these conditions. Numerous BrdU-labeled cells were still observed in the SVZ and RMS. The data show that focal cortical ischemia does not lead to the long-term survival of new neurons in the striatum or cortex but induces long-term alterations in the SVZ and the production of new oligodendrocytes that may contribute to neural repair.