Dentate gyrus neurogenesis after cerebral ischemia and behavioral training.

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.

Behaviorally-induced ultrastructural plasticity in the hippocampal region after cerebral ischemia.

Behavioral training has been shown to induce synaptic plasticity in both intact and injured animals. Because of the possibility that the adaptive changes after ischemic damage may make the brain more malleable to behavioral training, we examined the effects of complex environment (EC) housing and exercise (EX) after global cerebral ischemia on synaptic structural alterations. Forty-two adult male Wistar rats were included in the study and assigned to either ischemia or sham group. Following ischemic or sham surgery, rats were randomized to either EC, EX, or social condition (SC, paired housing) group. CA1 was processed for electron microscopy and unbiased stereological techniques were used to evaluate plasticity. Significantly decreased neuron density was seen in anterior and medial CA1 in ischemic animals regardless of behavioral training. Neuron density in anterior CA1 was 31% less than the medial area. Synaptogenesis was influenced by cerebral ischemia and behavioral training in that all ischemic groups and sham EC animals showed greater number of synapses per neuron compared to the sham EX and SC groups. Analysis of synapse configuration showed that the synaptogenesis in ischemia EX and SC rats was formed mainly by synapses with single synaptic boutons, whereas in the ischemia EC and sham EC rats synaptogenesis was formed mainly by synapses with multiple synaptic boutons. Furthermore, housing of sham and ischemia rats in EC resulted in increased number of synapses with perforated postsynaptic density. Together, these data suggest that behavioral experience in EC after insult may be able to enhance synaptic plasticity.