title: High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Improves Functional Recovery by Enhancing Neurogenesis and Activating BDNF/TrkB Signaling in Ischemic Rats.
abstract: Repetitive transcranial magnetic stimulation (rTMS) has rapidly become an attractive therapeutic approach for stroke. However, the mechanisms underlying this remain elusive. This study aimed to investigate whether high-frequency rTMS improves functional recovery mediated by enhanced neurogenesis and activation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway and to compare the effect of conventional 20 Hz rTMS and intermittent theta burst stimulation (iTBS) on ischemic rats. Rats after rTMS were sacrificed seven and 14 days after middle cerebral artery occlusion (MCAO), following evaluation of neurological function. Neurogenesis was measured using specific markers: Ki67, Nestin, doublecortin (DCX), NeuN and glial fibrillary acidic protein (GFAP), and the expression levels of BDNF were visualized by Western blotting and RT-PCR analysis. Both high-frequency rTMS methods significantly improved neurological function and reduced infarct volume. Moreover, 20 Hz rTMS and iTBS significantly promoted neurogenesis, shown by an increase of Ki67/DCX, Ki67/Nestin, and Ki67/NeuN-positive cells in the peri-infarct striatum. These beneficial effects were accompanied by elevated protein levels of BDNF and phosphorylated-TrkB. In conclusion, high-frequency rTMS improves functional recovery possibly by enhancing neurogenesis and activating BDNF/TrkB signaling pathway and conventional 20 Hz rTMS is better than iTBS at enhancing neurogenesis in ischemic rats.
authors.affiliation: Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China. jill_272@foxmail.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China. zhenghaiqing0909@aliyun.com.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China. zhangliying_good@126.com.
authors.forename: Liying
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China. zhangqingjie3415@163.com.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China. lovelyxt2008@163.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China. peizhong@mail.sysu.edu.cn.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Pei
authors.affiliation: Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China. xiquhu@hotmail.com.
authors.forename: Xiquan
authors.initials: X
authors.lastname: Hu
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000378:metabolism / Q000534:rehabilitation / Q000628:therapy; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism* / Q000534:rehabilitation* / Q000628:therapy; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D051381:Rats; D020813:Receptor, trkB / Q000378:metabolism*; D020127:Recovery of Function; D015398:Signal Transduction; D020521:Stroke; D050781:Transcranial Magnetic Stimulation / Q000379:methods
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D020813:Receptor, trkB
keywords: BDNF; MCAO; TrkB; neural stem cells; neurological function; rTMS