Long-term Effect Of Stroke On The Neurogenesis Of Dentate Gyrus In The Adult Rats

Objective: To investigate the long-term effect of transient cerebral ischemia on the cell proliferation and neurogenesis in the dentate gyrus (DG) of adult rats. Methods: The adult rats were induced to transient focal cerebral ischemia model with middle cerebral artery occlusion (MCAO) by the intraluminal filament technique, after two hours occlusion, the filament was withdrawn. Sequentially intraperitoneal injection of the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) to determine the extent of cell proliferation, and combined with single or double immunohistochemistry staining with antibodies BrdU, DCX (doublecortin), NeuN (neuronal nuclei), GFAP (glial fibrillary acidic protein) and PV (parvalbumin) in rats after the insult to phenotypic analysis and fate mapping the new born neurons, the colocalization were confirmed under the laser scanning confocal microscope. In the second experiment, rats received twice daily injections of BrdU for five consecutive days after six weeks recovery from MCAO induction, rats were sacrificed two or six weeks after the last BrdU injection.Results: From two weeks to six months after the transient MCAO, there were more DCX positive cells in the ipsilateral DG of the rats compared to the contralateral side. After the S-phase marker BrdU was injected to label newly generated cells two days after MCAO, a large number of BrdU-labeled neuroblasts differentiated into mature granular neurons. These BrdU-labeled neurons survived for at least six months. When BrdU was injected six weeks after the insult, there were still more newly generated neuroblasts differentiated into mature neurons in the ipsilateral DG compared to the contralateral DG.Conclusion: These data indicate that the transient cerebral ischemia initiates a prolonged increase in neurogenesis and promotes the normal development of the newly generated neurons in the adult dentate gyrus.