Long-Term Continuous Cervical Spinal Cord Stimulation Exerts Neuroprotective Effects in Experimental Parkinson’s Disease
Open Access
- 16 June 2020
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Aging Neuroscience
- Vol. 12, 164
- https://doi.org/10.3389/fnagi.2020.00164
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 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.This publication has 52 references indexed in Scilit:
- Peripheral Nerve Repair with Cultured Schwann Cells: Getting Closer to the ClinicsThe Scientific World Journal, 2012
- Change of the melanocortin system caused by bilateral subthalamic nucleus stimulation in Parkinson’s diseaseActa Neurologica Scandinavica, 2011
- Stimulation of the rat subthalamic nucleus is neuroprotective following significant nigral dopamine neuron lossNeurobiology of Disease, 2010
- SPINAL CORD STIMULATION FAILED TO RELIEVE AKINESIA OR RESTORE LOCOMOTION IN PARKINSON DISEASENeurology, 2010
- Spinal Cord Stimulation Restores Locomotion in Animal Models of Parkinson's DiseaseScience, 2009
- Bilateral Deep Brain Stimulation vs Best Medical Therapy for Patients With Advanced Parkinson DiseaseA Randomized Controlled TrialJAMA, 2009
- Roles of dorsal column pathway and transient receptor potential vanilloid type 1 in augmentation of cerebral blood flow by upper cervical spinal cord stimulation in ratsNeuroscience, 2008
- Incidence of symptomatic hemorrhage after stereotactic electrode placementJournal of Neurosurgery, 2007
- Adrenomedullin Gene Delivery Protects Against Cerebral Ischemic Injury by Promoting Astrocyte Migration and SurvivalHuman Gene Therapy, 2004
- Long-term stimulation of the subthalamic nucleus in hemiparkinsonian rats: neuroprotection of dopaminergic neuronsJournal of Neurosurgery, 2004