Music Therapy Alleviates Motor Dysfunction in Rats With Focal Cerebral Ischemia-Reperfusion Injury by Regulating BDNF Expression.

Music Therapy Alleviates Motor Dysfunction in Rats With Focal Cerebral Ischemia-Reperfusion Injury by Regulating BDNF Expression.
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音乐疗法通过调节 BDNF 表达减轻局灶性脑缺血再灌注损伤大鼠的运动功能障碍

DOI:
10.3389/fneur.2021.666311
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发表时间:
2021
影响因子:
3.4
通讯作者:
Gu JH
Gu JH
中科院分区:
医学3区
文献类型:
--
作者:
Chen W;Zheng J;Shen G;Ji X;Sun L;Li X;Xu F;Gu JH

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背景/目的:以音乐为基础的治疗在中枢神经系统疾病中发挥作用。本研究旨在探讨不同剂量、不同持续时间的音乐治疗对卒中后运动功能恢复的影响及其分子机制。方法:成年雄性SD大鼠大脑中动脉闭塞(MCAO)1h后再灌流。实验一:将MCAO术后存活1周的大鼠随机分为4组(每组10只):MCAO组、1h音乐组(Mozart K.448音乐治疗1h/d,持续2周)、12h音乐组(Mozart K.448音乐治疗12h/d,持续2周)和加速音乐组(反向加速音乐治疗12h,持续2周,AM组)。实验二将存活的大鼠随机分为3组:MCAO组、音乐12h组(音乐治疗12h/d,共3周)、MUSIC-R组(音乐治疗12h/d,共2周,休息1周)。从手术后第一天到实验结束,每天都要评估三个神经评分。实验2于MCAO术后3周处死大鼠,实验1或4周后处死大鼠,用尼氏染色观察梗死区、梗死区和运动皮质神经元的存活和再生情况。用Western印迹和免疫荧光方法检测脑源性神经营养因子(BDNF)和胶质纤维酸性蛋白(GFAP)在同侧大脑半球的表达和分布。结果:在不同音乐治疗剂量的实验中,与MCAO组比较,12h音乐组运动功能明显改善,而1h音乐组和AM组运动功能改善不明显。12h MUSIC组和1h MUSIC组同侧大脑半球运动皮质脑源性神经营养因子蛋白水平均高于MCAO组。音乐12h组神经元和尼氏小体明显多于MCAO组。免疫荧光分析显示,音乐治疗12h可诱导BDNF和GFAP在损伤边界积聚。在不同音乐治疗时间的实验中,音乐治疗3周(音乐12h组)比音乐干预2周(音乐-R组)诱导的细胞突触更长,细胞间连接更清晰。此外,12h MUSIC组胶质纤维酸性蛋白的形态与成熟激活的星形胶质细胞更为相似。结论:音乐疗法可长期改善卒中后运动功能,促进神经元修复。其机制可能是通过刺激受损运动皮质BDNF和GFAP的分泌来实现的。
Background/Aim: Music-based therapy plays a role in central nervous system diseases. We aimed to explore the effect of different doses and durations of music therapy on motor function recovery after stroke and the underlying molecular mechanisms. Methods: Adult male Sprague–Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h, which was followed by reperfusion. In experiment 1, the rats that survived 1 week after MCAO surgery were randomly allocated into four groups (n = 10 per group): MCAO group, 1 h music group (Mozart K.448 music therapy 1 h per day for 2 weeks), 12 h music group (Mozart K.448 music therapy 12 h/day for 2 weeks), and accelerated music group (reversely accelerated music therapy 12 h for 2 weeks, AM group). In experiment 2, the survived rats were randomly divied into three groups: MCAO group, 12 h music group (music therapy 12 h/day for 3 weeks), and 12 h music-R group (music therapy 12 h/day for 2 weeks and rest for 1 week). Three neuroscores were evaluated daily, starting on the first day after surgery until the end of the experiment. The rats were killed 3 weeks after MCAO surgery in experiment 1 or 4 weeks after surgery in experiment 2. Nissl staining of infart core, peri-infarct zone, and motor cortex was performed to assess neuronal survival and regeneration. Western blot and immunofluorescence were used to detect the expression and distribution of brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) in ipsilateral hemispheres. Results: In the experiment of different music therapy doses, the motor function in the 12-h music group but not in the 1-h music group and AM group was significantly improved compared with that of the MCAO group. The BDNF protein level of the ipsilateral hemisphere motor cortex in the 12-h music group and the 1-h music group was higher than that of the MCAO group. The neurons and Nissl bodies were more in the 12-h music group than in the MCAO group. Immunofluorescence assay showed that a 12 h music therapy induces BDNF and GFAP accumulation at the damage boundary. In the experiment of different music therapy durations, 3 weeks music therapy (12 h music group) induced more longer cell synapses and more clearer cell-to-cell connections than 2 weeks music intervention (12 h music-R group). Moreover, the GFAP morphology in the 12-h music group was more similar to mature activated astrocytes than that in the 12-h music-R group. Conclusions: Music therapy may improve poststroke motor function and promote neuronal repair in the long term. The mechanism may be through stimulating BDNF and GFAP secretion in the injured motor cortex.
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发表时间: 2008-01-01
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