Early Repetitive Transcranial Magnetic Stimulation Exerts Neuroprotective Effects and Improves Motor Functions in Hemiparkinsonian Rats

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. Acc...

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Main Authors: Tsung-Hsun Hsieh, Xiao-Kuo He, Hui-Hua Liu, Jia-Jin J. Chen, Chih-Wei Peng, Hao-Li Liu, Alexander Rotenberg, Ko-Ting Chen, Ming-Yuan Chang, Yung-Hsiao Chiang, Pi-Kai Chang, Chi-Wei Kuo
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2021/1763533
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author Tsung-Hsun Hsieh
Xiao-Kuo He
Hui-Hua Liu
Jia-Jin J. Chen
Chih-Wei Peng
Hao-Li Liu
Alexander Rotenberg
Ko-Ting Chen
Ming-Yuan Chang
Yung-Hsiao Chiang
Pi-Kai Chang
Chi-Wei Kuo
author_facet Tsung-Hsun Hsieh
Xiao-Kuo He
Hui-Hua Liu
Jia-Jin J. Chen
Chih-Wei Peng
Hao-Li Liu
Alexander Rotenberg
Ko-Ting Chen
Ming-Yuan Chang
Yung-Hsiao Chiang
Pi-Kai Chang
Chi-Wei Kuo
author_sort Tsung-Hsun Hsieh
collection DOAJ
description 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.
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spelling doaj-art-4ca4a40bb4ef4236addc5f1ca8dd0fdf2025-08-20T03:36:19ZengWileyNeural Plasticity1687-54432021-01-01202110.1155/2021/1763533Early Repetitive Transcranial Magnetic Stimulation Exerts Neuroprotective Effects and Improves Motor Functions in Hemiparkinsonian RatsTsung-Hsun Hsieh0Xiao-Kuo He1Hui-Hua Liu2Jia-Jin J. Chen3Chih-Wei Peng4Hao-Li Liu5Alexander Rotenberg6Ko-Ting Chen7Ming-Yuan Chang8Yung-Hsiao Chiang9Pi-Kai Chang10Chi-Wei Kuo11School of Physical Therapy and Graduate Institute of Rehabilitation ScienceDepartment of Rehabilitation MedicineDepartment of Rehabilitation MedicineDepartment of Biomedical EngineeringSchool of Biomedical EngineeringDepartment of Electrical EngineeringDepartment of NeurologyDepartment of NeurosurgeryDivision of NeurosurgeryDepartment of SurgerySchool of Physical Therapy and Graduate Institute of Rehabilitation ScienceSchool of Physical Therapy and Graduate Institute of Rehabilitation ScienceRepetitive 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.http://dx.doi.org/10.1155/2021/1763533
spellingShingle Tsung-Hsun Hsieh
Xiao-Kuo He
Hui-Hua Liu
Jia-Jin J. Chen
Chih-Wei Peng
Hao-Li Liu
Alexander Rotenberg
Ko-Ting Chen
Ming-Yuan Chang
Yung-Hsiao Chiang
Pi-Kai Chang
Chi-Wei Kuo
Early Repetitive Transcranial Magnetic Stimulation Exerts Neuroprotective Effects and Improves Motor Functions in Hemiparkinsonian Rats
Neural Plasticity
title Early Repetitive Transcranial Magnetic Stimulation Exerts Neuroprotective Effects and Improves Motor Functions in Hemiparkinsonian Rats
title_full Early Repetitive Transcranial Magnetic Stimulation Exerts Neuroprotective Effects and Improves Motor Functions in Hemiparkinsonian Rats
title_fullStr Early Repetitive Transcranial Magnetic Stimulation Exerts Neuroprotective Effects and Improves Motor Functions in Hemiparkinsonian Rats
title_full_unstemmed Early Repetitive Transcranial Magnetic Stimulation Exerts Neuroprotective Effects and Improves Motor Functions in Hemiparkinsonian Rats
title_short Early Repetitive Transcranial Magnetic Stimulation Exerts Neuroprotective Effects and Improves Motor Functions in Hemiparkinsonian Rats
title_sort early repetitive transcranial magnetic stimulation exerts neuroprotective effects and improves motor functions in hemiparkinsonian rats
url http://dx.doi.org/10.1155/2021/1763533
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