Long-Term Motor Cortical Electrical Stimulation Ameliorates 6-Hydroxydopamine-Induced Motor Dysfunctions and Exerts Neuroprotective Effects in a Rat Model of Parkinson's Disease

Chi-Wei Kuo; Ming-Yuan Chang; Ming-Yi Chou; Chien-Yuan Pan; Chih-Wei Peng; Hui-Chiun Tseng; Tsu-Yi Jen; Xiao-Kuo He; Hui-Hua Liu; Thi Xuan Dieu Nguyen; Pi-Kai Chang; Tsung-Hsun Hsieh

doi:10.3389/fnagi.2022.848380

Long-Term Motor Cortical Electrical Stimulation Ameliorates 6-Hydroxydopamine-Induced Motor Dysfunctions and Exerts Neuroprotective Effects in a Rat Model of Parkinson's Disease

Front Aging Neurosci. 2022 Feb 16:14:848380. doi: 10.3389/fnagi.2022.848380. eCollection 2022.

Authors

Chi-Wei Kuo^{1

2}, Ming-Yuan Chang^{3

4

5}, Ming-Yi Chou², Chien-Yuan Pan², Chih-Wei Peng⁶, Hui-Chiun Tseng², Tsu-Yi Jen⁷, Xiao-Kuo He⁸, Hui-Hua Liu⁹, Thi Xuan Dieu Nguyen¹, Pi-Kai Chang¹, Tsung-Hsun Hsieh^{1

10

11}

Affiliations

¹ School of Physical Therapy and Graduate Institute of Rehabilitation Science, Chang Gung University, Taoyuan City, Taiwan.
² Department of Life Science, National Taiwan University, Taipei City, Taiwan.
³ Division of Neurosurgery, Department of Surgery, Min-Sheng General Hospital, Taoyuan City, Taiwan.
⁴ Department of Early Childhood and Family Educare, Chung Chou University of Science and Technology, Yuanlin City, Taiwan.
⁵ Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei City, Taiwan.
⁶ School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City, Taiwan.
⁷ Department of Psychology, National Taiwan University, Taipei City, Taiwan.
⁸ Department of Rehabilitation Medicine, The Fifth Hospital of Xiamen, Xiamen, China.
⁹ Department of Rehabilitation Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
¹⁰ Neuroscience Research Center, Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
¹¹ Healthy Aging Research Center, Chang Gung University, Taoyuan City, Taiwan.

Abstract

Objective: Cortical electrical stimulation (CES) can modulate cortical excitability through a plasticity-like mechanism and is considered to have therapeutic potentials in Parkinson's disease (PD). However, the precise therapeutic value of such approach for PD remains unclear. Accordingly, we adopted a PD rat model to determine the therapeutic effects of CES. The current study was thus designed to identify the therapeutic potential of CES in PD rats.

Methods: A hemiparkinsonian rat model, in which lesions were induced using unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, was applied to identify the therapeutic effects of long-term (4-week) CES with intermittent theta-burst stimulation (iTBS) protocol (starting 24 h after PD lesion observation, 1 session/day, 5 days/week) on motor function and neuroprotection. After the CES intervention, detailed functional behavioral tests including gait analysis, akinesia, open-field locomotor activity, apomorphine-induced rotation as well as degeneration level of dopaminergic neurons were performed weekly up to postlesion week 4.

Results: After the CES treatment, we found that the 4-week CES intervention ameliorated the motor deficits in gait pattern, akinesia, locomotor activity, and apomorphine-induced rotation. Immunohistochemistry and tyrosine hydroxylase staining analysis demonstrated that the number of dopamine neurons was significantly greater in the CES intervention group than in the sham treatment group.

Conclusion: This study suggests that early and long-term CES intervention could reduce the aggravation of motor dysfunction and exert neuroprotective effects in a rat model of PD. Further, this preclinical model of CES may increase the scope for the potential use of CES and serve as a link between animal and PD human studies to further identify the therapeutic mechanism of CES for PD or other neurological disorders.

Keywords: 6-OHDA; Parkinson’s disease; cortical electrical stimulation; gait; locomotor function; neuroprotection; rats.