TY - JOUR
T1 - Long-Term Continuous Cervical Spinal Cord Stimulation Exerts Neuroprotective Effects in Experimental Parkinson’s Disease
AU - Kuwahara, Ken
AU - Sasaki, Tatsuya
AU - Yasuhara, Takao
AU - Kameda, Masahiro
AU - Okazaki, Yosuke
AU - Hosomoto, Kakeru
AU - Kin, Ittetsu
AU - Okazaki, Mihoko
AU - Yabuno, Satoru
AU - Kawauchi, Satoshi
AU - Tomita, Yousuke
AU - Umakoshi, Michiari
AU - Kin, Kyohei
AU - Morimoto, Jun
AU - Lee, Jea Young
AU - Tajiri, Naoki
AU - Borlongan, Cesar V.
AU - Date, Isao
N1 - Funding Information:
Funding. This research was supported by scientific research grants from the Ministry of Health, Labor, and Welfare of Japan (09156274 and 24592129). All data collection, analysis, writing, and submission decisions were made by the authors of this manuscript, not by funding sources.
Publisher Copyright:
© Copyright © 2020 Kuwahara, Sasaki, Yasuhara, Kameda, Okazaki, Hosomoto, Kin, Okazaki, Yabuno, Kawauchi, Tomita, Umakoshi, Kin, Morimoto, Lee, Tajiri, Borlongan and Date.
PY - 2020/6/16
Y1 - 2020/6/16
N2 - Background: Spinal 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. Objective: Recognizing the limitations of conventional stimulation, we now investigated the effects of continuous SCS in freely moving parkinsonian rats. Methods: We 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. Results: The 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. Conclusions: This 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.
AB - Background: Spinal 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. Objective: Recognizing the limitations of conventional stimulation, we now investigated the effects of continuous SCS in freely moving parkinsonian rats. Methods: We 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. Results: The 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. Conclusions: This 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.
KW - 6-hydroxydopamine
KW - electrical stimulation
KW - neuroinflammation
KW - neuromodulation
KW - neuroprotection
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U2 - 10.3389/fnagi.2020.00164
DO - 10.3389/fnagi.2020.00164
M3 - Article
AN - SCOPUS:85087162521
VL - 12
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
SN - 1663-4365
M1 - 164
ER -