Effects of recombinant adenovirus-mediated hypoxia-inducible factorlalpha 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-1α)gene on proliferation and differentiation of endogenous neural stem cells(NSCs)in rats following intracerebral hemorrhage(ICH)and the 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-1αwas 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(Brdtl)-,BrdU/DCX-,and BrdU/glial fibrillary acidic prolein-posilive cells in the subventricular zone were counted using immumofluorescence method among PBS,Ad,and Ad-HIF-1αgroups.Results:On the 7th,14th,21st and 28th d after ICH,neurological deficit scores in the Ad-HIF-1αgroup were significantly lower than in the PBS and Ad groups(P【0.05).In the Ad-HIF-lαgroup,DCX expression was significantly increased on the 7th d,peaked on the 14th d,and then gradually decreased.In the Ad-HIF-1αgroup,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-1αgroup was significantly greater than in the PBS and Ad groups(P【0.05).Conclusions:HIF-1αgene can promote the proliferation,migration and differentiation of endogenous neural stem cells after ICH,thereby contributing to neurofunctional recovery after ICH.