Neurogenesis by progenitor cells in the ischemic adult rat hippocampus

Background and Purpose-Recently, there has been great interest in adult neu rogenesis. We investigated whether transient forebrain ischemia could influ ence the proliferation of neuronal progenitor in the subgranular zone (SGZ) of the rat hippocampus and whether aging could influence the neurogenesis after ischemia. Methods-Male Wistar rats were subjected to 4-vessel occlusion model. We use d a bromodeoxyuridine (BrdU) labeling method to identify the postproliferat ion cells and double-immunostaining with confocal microscopy to determine t he cell phenotype. Results-The number of BrdU-positive cells in the SGZ increased approximate to5.7-fold 8 days after ischemia, compared with the control. BrdU-positive cells formed clusters. which suggested that these cells had divided from an original progenitor cell, and expressed Musashi I (Msi1), a marker of neur al stem/progenitor cells. Although astrocytes also expressed Msi1 in the ad ult brain, Msi1-positive cells that formed clusters in the SGZ did not expr ess glial fibrillary acidic protein, an astrocyte marker. About 70% of all BrdU-positive cells in the SGZ represented the neuronal phenotype 4 weeks a fter the BrdU injection. Although proliferation of progenitor cells was sti mulated in both young and older animals, aging accelerated the reduction in newborn cells after ischemia. Conclusions-Our results indicate that ischemic stress stimulated the prolif eration of neuronal progenitor cells in the SGZ of both young and old rats but resulted in increased neurogenesis only in young animals. Our findings will be important in developing therapeutic intervention to enhance endogen ous neurogenesis after brain injury.