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Functional electrical stimulation increases neural stem/progenitor cell proliferation and neurogenesis in the subventricular zone of rats with stroke

摘要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 immunofluorescence 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 wera subjected to oneway 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 flbrillary acidic protein doublepositive 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/mm2) was significantly increased compared with the control group ((262.58±35.11) cells/mm2,P <0.05) and the placebo group ((266.17±47.98) cells/mm2,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).Conclusion FES augments the proliferation,differentiation,and migration of NSCs and thus promotes neurogenesis,which may be related to the improvement of neurological outcomes.

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作者单位 Department of Rehabilitation Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120,China [1] Department of Rehabilitation Medicine, Sixth People's Hospital of Shenzhen, Shenzhen, Guangdong 518052, China [2] Department of Rehabilitation Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China [3] Department of Rehabilitation Medicine, Second Affiliated Hospital of Guangzhou Medical College, Guangzhou, Guangdong 510260, China [4]
栏目名称 ORIGINAL ARTICLES
DOI 10.3760/cma.j.issn.0366-6999.20130478
发布时间 2013-08-01
基金项目
This study was supported by China's National Natural Science Research Council
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中华医学杂志(英文版)

中华医学杂志(英文版)

2013年126卷12期

2361-2367页

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