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.
Highlights
Parkinson’s disease (PD) is a progressive neurodegenerative disease caused by the loss of dopaminergic neurons in the nigrostriatal system
Levodopa treatment remains the gold standard of treatment for PD, but only supportive effects are achieved with adverse effects over time [1] necessitating the need for innovative therapies
Laboratory studies have shown that spinal cord stimulation (SCS) increases cerebral blood flow in animal models of cerebral ischemia or spasms after subarachnoid hemorrhage through vasodilation effects with subsequent behavioral amelioration [3,4,5,6,7,8,9,10], and recently, a study demonstrated that SCS at the high thoracic level for PD model of rats has neuroprotective effects [11]
Summary
Parkinson’s disease (PD) is a progressive neurodegenerative disease caused by the loss of dopaminergic neurons in the nigrostriatal system. Deep brain stimulation is effective for motor symptoms of PD, but the inclusion criteria have been limited. In 2009, Fuentes and colleagues reported that spinal cord stimulation (SCS) restores locomotion in animal models of PD [2]. SCS is an alternative approach for treatment of neuropathic pain after medication has failed. Laboratory studies have shown that SCS increases cerebral blood flow in animal models of cerebral ischemia or spasms after subarachnoid hemorrhage through vasodilation effects with subsequent behavioral amelioration [3,4,5,6,7,8,9,10], and recently, a study demonstrated that SCS at the high thoracic level for PD model of rats has neuroprotective effects [11]
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