Abstract：OBJECTIVE: Many studies have demonstrated that neurogenesis is enhanced after cerebral ischemia in the adult rats. However, little is known about neurogenesis in the brain of neonatal rats after hypoxia-ischemia (HI). This study investigated neurogenesis in neonatal rats 1 and 4 weeks after HI. METHODS: Twenty-four seven-day-old Wistar rats were randomly assigned into Control group (n=8) and Experimental group (n=16). HI was induced by ligating the right common carotid artery combined with hypoxia exposure (8% oxygen in nitrogen) in the Experimental group. In the Control group, the right common carotid artery was isolated but not ligated and there was no exposure to hypoxia. MR imaging was performed 24 hrs after HI to confirm the formation of infarct. Bromodeoxyuridine (BrdU) was injected intraperitonally daily between 2-6 days after operation or HI to label newly generated cells in both groups. Neurogenesis was examined by immunofluorescence assay 1 and 4 weeks after HI. RESULTS: Subventricular zone (SVZ) was obviously enlarged in the ischemic hemisphere but not in the contralateral hemisphere in the Experimental group 1 or 4 weeks after HI. The number of BrdU positive cells in the SVZ of the ischemic hemisphere in the Experimental group increased significantly compared with that in the Control group or that in the contralateral hemisphere 1 week after HI (both P< 0.05). After 4 weeks of HI the number of BrdU positive cells in the ischemic hemisphere decreased compared with that 1 week after HI, but still remained significantly higher than that in the Control group (P<0.05). The number of BrdU positive cells in the subgranular zone (SGZ) of the ischemic hemisphere increased 1 week after HI, being significantly higher than that in the Control group (P<0.05). After 4 weeks of HI the number of BrdU positive cells in the SGZ of the ischemic hemisphere decreased compared with that 1 week after HI, but still was significantly higher than that in the Control group (P<0.05). Some scattered BrdU positive cells were observed in the striatum or cortex of the ischemic hemisphere, particularly in peri-infarct 1 or 4 weeks after HI. CONCLUSIONS: Similar to the brain of adult rats, neurogenesis is enhanced in the brain of neonatal rats following HI. This result suggests that immature brain may have the capacity for self-repair.
