title: Effects of recombinant adenovirus-mediated hypoxia-inducible factor-1alpha gene on proliferation and differentiation of endogenous neural stem cells in rats following intracerebral hemorrhage.
abstract: 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-1α 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-1α groups.
  
  
  RESULTS
  On the 7th, 14th, 21st and 28th d after ICH, neurological deficit scores in the Ad-HIF-1α group were significantly lower than in the PBS and Ad groups (P<0.05). In the Ad-HIF-1α group, DCX expression was significantly increased on the 7th d, peaked on the 14th d, and then gradually decreased. In the Ad-HIF-1α 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-1α group was significantly greater than in the PBS and Ad groups (P<0.05).
  
  
  CONCLUSIONS
  HIF-1α gene can promote the proliferation, migration and differentiation of endogenous neural stem cells after ICH, thereby contributing to neurofunctional recovery after ICH.
authors.affiliation: Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. mhwang777@163.com
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.forename: Li-Fen
authors.initials: LF
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Tang
authors.forename: Chang-Lin
authors.initials: CL
authors.lastname: Hu
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002543:Cerebral Hemorrhage / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D000089662:Doublecortin Protein; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: Adenovirus; Endogenous neural stem cells; Hypoxia-inducible factor-1alpha; Intracerebral hemorrhage