Long-Term Continuous Cervical Spinal Cord Stimulation Exerts Neuroprotective Effects in Experimental Parkinson’s Disease

Frontiers in Aging Neuroscience

Isao Date¹  Ken Kuwahara¹  Michiari Umakoshi¹  Kyohei Kin¹  Masahiro Kameda¹  Ittetsu Kin¹  Mihoko Okazaki¹  Yousuke Tomita¹  Tatsuya Sasaki¹  Satoshi Kawauchi¹  Yosuke Okazaki¹  Takao Yasuhara¹  Kakeru Hosomoto¹  Satoru Yabuno¹  Jun Morimoto¹  Naoki Tajiri²  Jea-Young Lee³  Cesar V. Borlongan³ 

[1] Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan;Department of Neurophysiology and Brain Science, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan;Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL, United States;

关键词: electrical stimulation;    neuroinflammation;    neuromodulation;    neuroprotection;    6-hydroxydopamine;   

DOI  :  10.3389/fnagi.2020.00164

来源: DOAJ

【 摘 要 】

BackgroundSpinal cord stimulation (SCS) exerts neuroprotective effects in animal models of Parkinson’s disease (PD). Conventional stimulation techniques entail limited stimulation time and restricted movement of animals, warranting the need for optimizing the SCS regimen to address the progressive nature of the disease and to improve its clinical translation to PD patients.ObjectiveRecognizing the limitations of conventional stimulation, we now investigated the effects of continuous SCS in freely moving parkinsonian rats.MethodsWe developed a small device that could deliver continuous SCS. At the start of the experiment, thirty female Sprague-Dawley rats received the dopamine (DA)-depleting neurotoxin, 6-hydroxydopamine, into the right striatum. The SCS device was fixed below the shoulder area of the back of the animal, and a line from this device was passed under the skin to an electrode that was then implanted epidurally over the dorsal column. The rats were divided into three groups: control, 8-h stimulation, and 24-h stimulation, and behaviorally tested then euthanized for immunohistochemical analysis.ResultsThe 8- and 24-h stimulation groups displayed significant behavioral improvement compared to the control group. Both SCS-stimulated groups exhibited significantly preserved tyrosine hydroxylase (TH)-positive fibers and neurons in the striatum and substantia nigra pars compacta (SNc), respectively, compared to the control group. Notably, the 24-h stimulation group showed significantly pronounced preservation of the striatal TH-positive fibers compared to the 8-h stimulation group. Moreover, the 24-h group demonstrated significantly reduced number of microglia in the striatum and SNc and increased laminin-positive area of the cerebral cortex compared to the control group.ConclusionsThis study demonstrated the behavioral and histological benefits of continuous SCS in a time-dependent manner in freely moving PD animals, possibly mediated by anti-inflammatory and angiogenic mechanisms.

【 授权许可】

Unknown