帕金森氏症為一常見之老年人神經退化疾病。帕金森氏症患者依不同的嚴重程度承受像是肌肉僵直，顫抖和步態不穩等長期之運動功能障礙，並表現出神經可塑性和運動皮質神經調節缺失等問題。不同地皮質刺激技術像是重複性經顱磁刺激(rTMS)或皮質電刺激(CES)已被日益地發展，經由類似可塑性機制去調節皮質興奮性，其被認為對於帕金森氏症是具有治療潛力的。然而，像是皮質刺激這種治療方法在帕金森氏症上，目前仍然是不清楚且具有爭議的。因此，疾病動物模型有助於降低差異且提供了皮質刺激之機制了解在未來目標性突觸可塑性的治療應用。為了更了解皮質刺激之治療效果的神經機制並將研究轉至嚙齒動物疾病模型上，模擬重複性經顱磁刺激之皮質電刺激技術首度被發展於大鼠身上。此外，藉此種模型幫助下，經由運動行為和電生理技術來測試其慢性帕金森氏症大鼠在四週皮質陣發型電刺激模式下之治療效果。與重複性經顱磁刺激結果相同，在正常大鼠實驗下，間歇性陣發型刺激成功地使動作誘發電位上升，而在連續性陣發型刺激下，動作誘發電位則呈現下降。經過四周時間的觀察，比較陣發型皮質電刺激於慢性帕金森氏症大鼠在長期治療與偽治療下，結果發現陣發型皮質電刺激治療逐步地改善了步行速度和步長之運動功能。此外，藉由陣發型皮質電刺激所誘發之運動可塑性顯示，在偽治療下之運動可塑性仍為缺損情況，但在陣發型皮質電刺激長期治療下之運動可塑性則傾向接近正常大鼠之可塑性變化。綜合以上結果，本研究發展一動物模型來測試皮質電刺激所誘發出的動作可塑性，並進一步運用於帕金森氏症大鼠之長期治療上。有了此動物模型之幫助下，我們發現在陣發型皮質電刺激治療後，運動功能障礙和運動可塑性受損的情形有降低之趨勢。發展陣發型皮質電刺激之動物模型可用來當作人類和動物實驗的轉移銜接平台，並發展出像是重複性經顱磁刺激或皮質電刺激對帕金森氏症或其他神經疾病之皮質刺激治療方式。

Parkinson's disease (PD) is one of most common neurodegenerative diseases of the elderly which affects approximately seven million people worldwide and thirty thousand people in Taiwan. Individuals with different severities of Parkinson's disease (PD) suffer long lasting motor dysfunctions such as muscular rigidity, tremor and gait disturbance which also exhibits. The impairments of neuroplasticity and neuromodulation of motor cortex. Various cortical stimulation techniques such as repetitive magnetic stimulation (rTMS) or cortical electrical stimulation (CES), have been developed for modulating cortical excitability through plasticity-like mechanisms which are considered having therapeutic potentials for PD. However, the therapeutic value of such cortical stimulation approach for PD is still unclear and controversial. Accordingly, a disease animal model would be helpful to reduce the discrepancy and provide insights of cortical stimulation for future therapeutic applications targeting synaptic plasticity. To better understand the neural mechanism underlying the therapeutic effects of cortical stimulation and to enable translational research in rodent disease models, the CES module mimicking rTMS was first developed in rats. Furthermore, with the help of this model, the therapeutic effects of four weeks CES-theta burst stimulation (TBS) intervention were examined from motor behavioral and electrophysiological findings in advanced PD rats. In parallel with previous rTMS results, intermittent TBS (iTBS) successfully increased motor evoked potentials (MEPs), while MEPs suppressed after continuous TBS (cTBS) in healthy rats. For long-term effects of CES-TBS in chronic PD rats, in comparison with sham-treatment PD group, CES-TBS treatment progressively improved locomotor function in walking speed and step length over a 4-week time-course of observation. Furthermore, the motor plasticity induced by CES-TBS showed that the amount of motor plasticity were impaired in sham treatment PD rats but relatively evident in long-term CES treated PD group. In conclusion, an animal model for testing CES-induced motor plasticity in vivo has been developed for testing the beneficial effects of long-term CES treatment in PD rats. With the help of this model, we showed that the motor dysfunction and impaired motor plasticity can be reduced after CES-TBS treatment. The developed CES-TBS animal model may serve as a translational platform bridging human and animal studies for developing therapeutic strategies of cortical stimulation such as rTMS or CES for PD or other neurological disorders.

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