title: Functional electrical stimulation increases neural stem/progenitor cell proliferation and neurogenesis in the subventricular zone of rats with stroke.
abstract: BACKGROUND
  Functional electrical stimulation (FES) is known to promote the recovery of motor function in rats with ischemia and to upregulate the expression of growth factors which support brain neurogenesis. In this study, we investigated whether postischemic FES could improve functional outcomes and modulate neurogenesis in the subventricular zone (SVZ) after focal cerebral ischemia.
  
  
  METHODS
  Adult male Sprague-Dawley rats with permanent middle cerebral artery occlusion (MCAO) were randomly assigned to the control group, the placebo stimulation group, and the FES group. The rats in each group were further assigned to one of four therapeutic periods (1, 3, 7, or 14 days). FES was delivered 48 hours after the MCAO procedure and divided into two 10-minute sessions on each day of treatment with a 10-minute rest between them. Two intraperitoneal injections of bromodeoxyuridine (BrdU) were given 4 hours apart every day beginning 48 hours after the MCAO. Neurogenesis was evaluated by immunofuorescence staining. Wnt-3 which is strongly implicated in the proliferation and differentiation of neural stem cells (NSCs) was investigated by Western blotting analysis. The data were subjected to one- way analysis of variance (ANOVA), followed by a Tukey/Kramer or Dunnett post hoc test.
  
  
  RESULTS
  FES significantly increased the number of BrdU-positive cells and BrdU/glial fibrillary acidic protein double- positive neural progenitor cells in the SVZ on days 7 and 14 of the treatment (P < 0.05). The number of BrdU/doublecortin (DCX) double-positive migrating neuroblast cells in the ipsilateral SVZ on day 14 of the FES treatment group ((522.77 ± 33.32) cells/mm(2)) was significantly increased compared with the control group ((262.58 ± 35.11) cells/mm(2), P < 0.05) and the placebo group ((266.17 ± 47.98) cells/mm(2), P < 0.05). However, only a few BrdU/neuron-specific nuclear protein-positive cells were observed by day 14 of the treatment. At day 7, Wnt-3 was upregulated in the ipsilateral SVZs of the rats receiving FES ((0.44 ± 0.05)%) compared with those of the control group rats ((0.31 ± 0.02)%, P < 0.05) or the placebo group rats ((0.31 ± 0.04)%, P < 0.05). At day 14, the corresponding values were (0.56 ± 0.05)% in the FES group compared with those of the control group rats ((0.50 ± 0.06)%, P < 0.05) or the placebo group rats ((0.48 ± 0.06)%, P < 0.05).
  
  
  CONCLUSIONS
  FES augments the proliferation, differentiation, and migration of NSCs and thus promotes neurogenesis, which may be related to the improvement of neurological outcomes.
authors.affiliation: Department of Rehabilitation Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China.
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiang
authors.forename: Tie-Bin
authors.initials: TB
authors.lastname: Yan
authors.forename: Zhi-Mei
authors.initials: ZM
authors.lastname: Tan
authors.forename: Sheng-Huo
authors.initials: SH
authors.lastname: Li
authors.forename: Xiao-Kuo
authors.initials: XK
authors.lastname: He
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D002552:Cerebral Ventricles / Q000503:physiopathology*; D000089662:Doublecortin Protein; D004599:Electric Stimulation Therapy; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D008297:Male; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000503:physiopathology / Q000628:therapy*; D060509:Wnt3A Protein / Q000032:analysis
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D060509:Wnt3A Protein; D001973:Bromodeoxyuridine