Objective: To investigate the periodic quantity variation of proliferating neuronal progenitors after global brain ischemia and provide evidence for choosing the time-window of drug therapy to promote neuronal regeneration after ischemia.
Methods: Adult male Wistar rats were subjected to 15-min global brain ischemia (four-vessel occlusion model) and randomized subsequently into 8 groups (n=3). The rats were given intraperitoneal injections of BrdU (75 mg/kg) for 4 times daily (at a 2-hour interval) since day 7 till day 11 after ischemia, and on day 29, the rats were perfused transcardially for fixation. Another 3 normal rats were given BrdU in the same manner and killed the next day. Coronal sections of the brain tissue (30 microm) were prepared for immunocytochemical detection of BrdU-labeled cells and immunofluorescent detection of BrdU/NeuN double-labeled cells. The density of BrdU-positive cells and BrdU/NeuN double-labeled cells in the hippocampal dentate gyrus (DG) and CA1 region were counted and the density of proliferating cells at different days after ischemia were compared using one-way ANOVA.
Results: The proliferation of the neuronal progenitors increased after global brain ischemia. The number of BrdU-positive cells in the DG and CA1 region decreased gradually in 7-10 days after ischemia, and reached the normal level during 11-14 days. The differentiation of the progenitors did not vary after ischemia.
Conclusion: Increased proliferation of the neuroprogenitors occurs mainly within the initial 10 days after global ischemia in rats.