Dentate Gyrus Neurogenesis after Cerebral Ischemia and Behavioral Training

Abstract

Neurogenesis in the mammalian brain continues throughout adulthood. Several factors have been shown to influence neurogenesis, including experience in a complex environment (EC), exercise (EX), and ischemic insult. The authors investigated the effects of behavioral rehabilitation training following transient global cerebral ischemia on the number of new cells in the dentate gyrus that incorporated bromodeoxyuridine (BrdU), a thymidine analog that labels cells undergoing DNA replication. Seventy-two animals were included in the study, and 4-vessel occlusion was used to induce cerebral ischemia while control animals were subjected to anesthesia and sham surgery alone. Within 3 days of surgery, rats were randomly assigned to either EC, EX, or control (paired housing in standard laboratory conditions) groups. All animals were sacrificed 2 weeks after behavioral training. Immunohistochemistry results showed an increased number of BrdU-labeled cells in the subgranular zone of the dentate gyrus in all ischemic groups and in the EC and EX sham groups, although no significant group differences were seen. Examination of cell phenotype showed that almost all BrdU-positive cells colabeled with TuJ1, an immature neuron marker, in all animals whereas only a few BrdU-positive cells colabeled with NeuN, a mature neuron marker. BrdU/NeuN-labeled cells were seen only in the sham and ischemia EC groups. No new cells showed glial fibrillary acidic protein, astrocyte marker, colabeling. These results suggest that the adult brain has an inherent regenerative capacity after insult and that behavioral training following injury does not have an additive effect on neurogenesis. Finally, the enhanced maturation of BrdU-positive cells seen in the EC rats is probably modulated by environmental cues.