Effects of recombinant adenovirus mediated hypoxia inducible factor 1alpha gene on proliferation and differentiation of endogenous neural stem cells in rats following intracerebral hemorrhage

Objective: To investigate the effects of adenovirus (Ad) mediated hypoxia inducible factor 1alpha (HIF-1 alpha) gene on proliferation and differentiation of endogenous neural stem cells (NSCs) in rats following intracerebral hemorrhage (ICH) and tire underlying mechanisms. Methods: A total of 120 specific pathogen free, adult, male Sprague Dawley rats were included in this study. After establishment of ICH models in rats, PBS. Ad, or Ad HIF-1 alpha was administered via the ischemic ventricle. On the 1st, 7th, 14th, 21st and 28th d after ICH, rat neurological deficits were scored, doublecortin (DCX) expression in the subventricular zone cells was detected by immunohistochemical staining, and 5-bromo-2'-deoxyuridine (BrdU), BrdU/DCX, and BrdU/glial fibrillary acidic protein positive cells in the subventricular zone were counted using immumofluorescence method among PBS, Ad, and Ad HIF-1 alpha groups. Results: On the 7th, 14th, 21st and 28th d after ICH, neurological deficit scores in the Ad HIF-1 alpha group were significantly lower than in the PBS and Ad groups (P<0.05). In the Ad HIP-1 alpha group, DCX expression was significantly increased on the 7th d, peaked on the 14th d, and then gradually decreased. In the Ad HIF-1 alpha group, BrdU-positive cells were significantly increased over time course, and significant difference in BrdU-positive cell counts was observed when compared with the PBS and Ad groups at each time point (P<0.01 or 0.05). On the 7th, 14th, 21st and 28th d after ICH, the number of DCX, BrdU, BrdU/DCX, and BrdU/DCX positive cells in the Ad HIF-1 alpha group was significantly greater than in the PBS and Ad groups (P<0.05). Conclusions: HIF-1 alpha gene can promote the proliferation, migration and differentiation of endogenous neural stem cells after ICH, thereby contributing to neurofunctional recovery after ICH.