School of Physical Therapy and Graduate Institute of Rehabilitation Science, Chang Gung University, Taoyuan, Taiwan.
Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
Neural Plast. 2021 Dec 27;2021:1763533. doi: 10.1155/2021/1763533. eCollection 2021.
Repetitive transcranial magnetic stimulation (rTMS) is a popular noninvasive technique for modulating motor cortical plasticity and has therapeutic potential for the treatment of Parkinson's disease (PD). However, the therapeutic benefits and related mechanisms of rTMS in PD are still uncertain. Accordingly, preclinical animal research is helpful for enabling translational research to explore an effective therapeutic strategy and for better understanding the underlying mechanisms. Therefore, the current study was designed to identify the therapeutic effects of rTMS on hemiparkinsonian rats. A hemiparkinsonian rat model, induced by unilateral injection of 6-hydroxydopamine (6-OHDA), was applied to evaluate the therapeutic potential of rTMS in motor functions and neuroprotective effect of dopaminergic neurons. Following early and long-term rTMS intervention with an intermittent theta burst stimulation (iTBS) paradigm (starting 24 h post-6-OHDA lesion, 1 session/day, 7 days/week, for a total of 4 weeks) in awake hemiparkinsonian rats, the effects of rTMS on the performance in detailed functional behavioral tests, including video-based gait analysis, the bar test for akinesia, apomorphine-induced rotational analysis, and tests of the degeneration level of dopaminergic neurons, were identified. We found that four weeks of rTMS intervention significantly reduced the aggravation of PD-related symptoms post-6-OHDA lesion. Immunohistochemically, the results showed that tyrosine hydroxylase- (TH-) positive neurons in the substantia nigra pars compacta (SNpc) and fibers in the striatum were significantly preserved in the rTMS treatment group. These findings suggest that early and long-term rTMS with the iTBS paradigm exerts neuroprotective effects and mitigates motor impairments in a hemiparkinsonian rat model. These results further highlight the potential therapeutic effects of rTMS and confirm that long-term rTMS treatment might have clinical relevance and usefulness as an additional treatment approach in individuals with PD.
重复经颅磁刺激（rTMS）是一种调节运动皮质可塑性的热门非侵入性技术，具有治疗帕金森病（PD）的潜力。然而，rTMS 在 PD 中的治疗益处和相关机制仍不确定。因此，临床前动物研究有助于使转化研究能够探索有效的治疗策略，并更好地了解潜在的机制。因此，本研究旨在确定 rTMS 对偏侧帕金森病大鼠的治疗作用。采用单侧注射 6-羟多巴胺（6-OHDA）诱导的偏侧帕金森病大鼠模型，评估 rTMS 在运动功能和多巴胺能神经元神经保护作用中的治疗潜力。在清醒的偏侧帕金森病大鼠中，采用间歇 theta 爆发刺激（iTBS）方案（6-OHDA 损伤后 24 小时开始，每天 1 次，每周 7 天，共 4 周）进行早期和长期 rTMS 干预后，评估 rTMS 对详细功能行为测试的影响，包括基于视频的步态分析、运动不能的棒测试、阿朴吗啡诱导的旋转分析以及多巴胺能神经元退变水平的测试。我们发现，4 周的 rTMS 干预显著减轻了 6-OHDA 损伤后 PD 相关症状的加重。免疫组织化学结果显示，rTMS 治疗组黑质致密部（SNpc）酪氨酸羟化酶（TH）阳性神经元和纹状体纤维明显保存。这些发现表明，采用 iTBS 方案的早期和长期 rTMS 具有神经保护作用，并减轻了偏侧帕金森病大鼠模型的运动障碍。这些结果进一步强调了 rTMS 的潜在治疗效果，并证实长期 rTMS 治疗可能具有临床相关性和实用性，可作为 PD 患者的附加治疗方法。
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