Role of Brain-Derived Neurotrophic Factor in Beneficial Effects of Repetitive Transcranial Magnetic Stimulation for Upper Limb Hemiparesis after Stroke
Role of Brain-Derived Neurotrophic Factor in Beneficial Effects of Repetitive Transcranial Magnetic Stimulation for Upper Limb Hemiparesis after Stroke
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DOI：
10.1371/journal.pone.0152241
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发表时间：
2016-03-23
期刊：
影响因子：
3.7
通讯作者：
Abo, Masahiro
中科院分区：
文献类型：
--
作者：
Niimi, Masachika;Hashimoto, Kenji;Abo, Masahiro
研究背景重复经颅磁刺激（repetitivetranscranialmagneticstimulation，rTMS）可改善脑卒中后上肢轻偏瘫，但其作用机制尚不清楚。目的探讨rTMS对脑卒中后偏瘫患者血清BDNF及其前体蛋白proBDNF和基质金属蛋白酶-9（MMP-9）水平的影响。62例患者接受康复加rTMS联合治疗，33例患者接受康复单药治疗，不接受rTMS治疗14天。1 Hz rTMS应用于非病变半球上第一骨间背侧肌的运动表征。采用Fugl-Meyer评定法和Wolf运动功能评定法（WMFT）对干预前后患侧上肢运动功能进行评定。收集血液样本进行BDNF多态性分析和测量BDNF，proBDNF和MMP-9 levels.Results2周的联合治疗增加BDNF和MMP-9血清水平，但不血清proBDNF。血清BDNF和MMP-9水平与运动功能改善无关，尽管基线血清proBDNF水平与WMFT改善呈负相关且显著（rho =-0.422，p = 0.002）。BDNF基因polymorphis.ConclusionsThe康复加低频rTMS的组合治疗似乎改善运动功能，在患肢，激活BDNF处理的结果rTMS治疗没有改变。BDNF及其前体proBDNF可能是脑卒中后运动功能恢复的潜在生物标志物。
BackgroundRepetitive transcranial magnetic stimulation (rTMS) can improve upper limb hemiparesis after stroke but the mechanism underlying its efficacy remains elusive. rTMS seems to alter brain-derived neurotrophic factor (BDNF) and such effect is influenced by BDNF gene polymorphism.ObjectivesTo investigate the molecular effects of rTMS on serum levels of BDNF, its precursor proBDNF and matrix metalloproteinase-9 (MMP-9) in poststroke patients with upper limb hemiparesis.MethodsPoststroke patients with upper limb hemiparesis were studied. Sixty-two patients underwent rehabilitation plus rTMS combination therapy and 33 patients underwent rehabilitation monotherapy without rTMS for 14 days at our hospital. One Hz rTMS was applied over the motor representation of the first dorsal interosseous muscle on the non-lesional hemisphere. Fugl-Meyer Assessment and Wolf Motor Function (WMFT) were used to evaluate motor function on the affected upper limb before and after intervention. Blood samples were collected for analysis of BDNF polymorphism and measurement of BDNF, proBDNF and MMP-9 levels.ResultsTwo-week combination therapy increased BDNF and MMP-9 serum levels, but not serum proBDNF. Serum BDNF and MMP-9 levels did not correlate with motor function improvement, though baseline serum proBDNF levels correlated negatively and significantly with improvement in WMFT (rho = -0.422, p = 0.002). The outcome of rTMS therapy was not altered by BDNF gene polymorphism.ConclusionsThe combination therapy of rehabilitation plus low-frequency rTMS seems to improve motor function in the affected limb, by activating BDNF processing. BDNF and its precursor proBDNF could be potentially suitable biomarkers for poststroke motor recovery.