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

Abstract

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

An Examination of mobile spinal cord stimulators on treating Parkinson disease

“…In a recent study, small mobile devices for continuous SCS in freely moving parkinsonian rats were developed. [ 20 ] The research demonstrated both an effective delivery of SCS by a small mobile device and a time-dependency on neuroprotective effects of rats of the PD. Both groups of SCS treated rats typically had improved performance in both contralateral bias and methamphetamine rotation tests; however, the 24-hour stimulation group exhibited better therapeutic effects than the 8-hour stimulation group.…”

“…Such a system has already been demonstrated to be effective for DBS in PD animals and now a lightweight, continuous SCS mobile device has also been developed. [ 18 19 20 ] This method achieves minimum invasiveness, free movement with a wireless system, readily accessible adjustment of stimulation conditions, and robust, stable stimulation in PD animals for at least 2 weeks [ Figure 1 ]. Of note, Bluetooth signaling efficiently controlled stimulation parameters.…”

“…The diminished activation of microglial cells by sustained SCS therapy indicates that gradual detrimental neuroinflammation can accompany PD, requiring sustained treatment to isolate cell death pathways effectively. [ 20 ]…”

On the Right Track to Treat Movement Disorders: Promising Therapeutic Approaches for Parkinson’s and Huntington’s Disease

“…Furthermore, both studies showed a positive effect in preserving the dopaminergic innervation of the striatum, reducing its loss by 30–35%. Recently, an investigation showed that continuous application of SCS (24 h ON SCS), starting immediately after injection of 6-OHDA, reduced the loss of dopaminergic neurons and their striatal projections by ~35% and ~32% respectively, while a regular SCS protocol (8 h SCS ON/16 h SVS OFF) counteracted the degeneration of the nigrostriatal dopaminergic pathway only by ~23% (Kuwahara et al, 2020 ). Thus, the periodicity of the treatment application reflects on different degrees of neuroprotection (Kuwahara et al, 2020 ).…”

“…Recently, an investigation showed that continuous application of SCS (24 h ON SCS), starting immediately after injection of 6-OHDA, reduced the loss of dopaminergic neurons and their striatal projections by ~35% and ~32% respectively, while a regular SCS protocol (8 h SCS ON/16 h SVS OFF) counteracted the degeneration of the nigrostriatal dopaminergic pathway only by ~23% (Kuwahara et al, 2020 ). Thus, the periodicity of the treatment application reflects on different degrees of neuroprotection (Kuwahara et al, 2020 ). These data suggest that SCS could have a neuroprotective effect that might contribute to the relief of the observed motor symptoms in PD, given the relevance of dopaminergic projections in modulating the functioning of the circuit of the nuclei of the base through the regulation of cortical and subcortical neuronal activity during movement (Gerfen and Surmeier, 2011 ; Canessa et al, 2016 ).…”