Spinal Cord Stimulation Exerts Neuroprotective Effects against Experimental Parkinson’s Disease

Abstract

In clinical practice, deep brain stimulation (DBS) is effective for treatment of motor symptoms in Parkinson’s disease (PD). However, the mechanisms have not been understood completely. There are some reports that electrical stimulation exerts neuroprotective effects on the central nervous system diseases including cerebral ischemia, head trauma, epilepsy and PD, although there are a few reports on neuroprotective effects of spinal cord stimulation (SCS). We investigated the neuroprotective effects of high cervical SCS on PD model of rats. Adult female Sprague-Dawley rats received hour-long SCS (2, 50 or 200 Hz) with an epidural electrode at C1–2 level for 16 consecutive days. At 2 days after initial SCS, 6-hydroxydopamine (6-OHDA) was injected into the right striatum of rats. Behavioral evaluations of PD symptoms were employed, including cylinder test and amphetamine-induced rotation test performed at 1 and 2 weeks after 6-OHDA injection. Animals were subsequently euthanized for immunohistochemical investigations. In order to explore neurotrophic and growth factor upregulation induced by SCS, another cohort of rats that received 50 Hz SCS was euthanized at 1 and 2 weeks after lesion for protein assays. Behavioral tests revealed that the number of amphetamine-induced rotations decreased in SCS groups. Immunohistochemically, tyrosine hydroxylase (TH)-positive fibers in the striatum were significantly preserved in SCS groups. TH-positive neurons in the substantia nigra pars compacta were significantly preserved in 50 Hz SCS group. The level of vascular endothelial growth factor (VEGF) was upregulated by SCS at 1 week after the lesion. These results suggest that high cervical SCS exerts neuroprotection in PD model of rats, at least partially by upregulation of VEGF. SCS is supposed to suppress or delay PD progression and might become a less invasive option for PD patients, although further preclinical and clinical investigations are needed to confirm the effectiveness and safety.

Electrical stimulation of the dorsal columns of the spinal cord for Parkinson's disease

“…Following these initial studies, other laboratories have independently validated our animal findings . In parallel, during the past 7 years, several independent clinical studies in PD patients with abnormal posture and gait disturbances have demonstrated positive results with DCS …”

“…Remarkably, such a neuroprotective effect was achieved by delivering DCS for 30 minutes, twice a week only, suggesting that better effects could be produced by more frequent therapy. These results have now been replicated independently by another laboratory, which reported that 1 hour/day of DCS, delivered for 16 consecutive days, resulted in the improvement of PD symptoms and the significant preservation of tyrosine hydroxylase (TH) fibers in the striatum and TH‐positive neurons in the SNc. Although the cellular mechanism underlying this putative long‐term neuroprotective action of DCS remains to be investigated, Shinko and colleagues also reported that DCS treatment upregulated the levels of vascular endothelial growth factor, a finding that could account, at least partially, for the observed neuroprotective effects.…”

Spinal Cord Stimulation in Patients With Complex Regional Pain Syndrome: A Possible Target for Immunomodulation?

“…The vasodilation at 500 Hz stimulation is caused by the activation of fibers that contain TRPV1 and the release of CGRP . Another animal study with a Parkinson's Disease rat model showed that the application of high cervical SCS increased levels of VEGF in the lesioned striatum and thereby exerting its neuroprotective effects . Furthermore, the neuroprotective effects seemed optimal with 50 Hz SCS when compared with 2 Hz and 200 Hz SCS.…”

The Protective Effect of Spinal Cord Stimulation Postconditioning Against Spinal Cord Ischemia/Reperfusion Injury in Rabbits

“…In the present study, the protective effects of SCS postconditioning at two frequencies (2 Hz and 50 Hz) were assessed. The 50 Hz SCS was selected because it is conventionally used in both clinical and experimental studies of pain treatment and has also been reported to augment cerebral blood flow markedly , reduce stroke volume in permanent middle cerebral artery (MCA) occlusion rats , inhibit myocardial apoptosis and reduce expression of caspase‐3 after cardiac ischemia/reperfusion , and ameliorate Parkinson symptoms and immunohistochemical changes in Parkinson's disease (PD) rats. Low frequency SCS (below 5 Hz) has also been used in researches.…”