Spinal Cord Stimulation Restores Locomotion in Animal Models of Parkinson's Disease

Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
Science (Impact Factor: 33.61). 04/2009; 323(5921):1578-82. DOI: 10.1126/science.1164901
Source: PubMed


Dopamine replacement therapy is useful for treating motor symptoms in the early phase of Parkinson's disease, but it is less effective in the long term. Electrical deep-brain stimulation is a valuable complement to pharmacological treatment but involves a highly invasive surgical procedure. We found that epidural electrical stimulation of the dorsal columns in the spinal cord restores locomotion in both acute pharmacologically induced dopamine-depleted mice and in chronic 6-hydroxydopamine-lesioned rats. The functional recovery was paralleled by a disruption of aberrant low-frequency synchronous corticostriatal oscillations, leading to the emergence of neuronal activity patterns that resemble the state normally preceding spontaneous initiation of locomotion. We propose that dorsal column stimulation might become an efficient and less invasive alternative for treatment of Parkinson's disease in the future.

Download full-text


Available from: Per Petersson,
40 Reads
  • Source
    • "From 1999 to 2004, clinical cases showed that the therapeutic effect lasts about 4–6 months on average [2]. To make treatments more permanent, implantable neural electrical stimulation systems have been developed to make the system more viable to treat various disorders, such as for Parkinson's disease [3] and sciatica [4] [5]. To address the invasiveness of implanting surgeries, minimally invasive surgery (MIS) procedures have been developed, which aim to reduce the size of incisions as well as a patient's discomfort after an operation [6]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A bipolar electrode probe used for implantable nerve stimulation treatments in minimally invasive surgeries is presented. The probe is composed of a flexible printed circuit substrate and a patterned SU-8 film. This probe features a three-dimensional (3D) tweezer-like mechanism opened by residual stress from the SU-8 film, designed to fix the probe in the tissue surrounding a target nerve. Stripes on the SU-8 film direct the net residual stress in a single direction to form a curve. The holding strengths of the probes with different deformations are defined and measured by a tensile test. Results show that the fixing ability of a 3D probe is better than a plane probe. The probes with curvature heights between 13 and 14 mm have a maximum average breaking force of 0.258 N, which is 16.3 and 13.1% higher than the probes with curvature heights between 9 and 10 mm and between 10 and 11 mm, respectively. In addition, a film of gelatin fibrous membrane, produced by electrospinning, covers the fixed ends of the probe's anchors and acts as cell scaffolds to induce cell growth, which help to ensure long-term fixation in the body. 3T3 fibroblast cells are grown to verify the scaffold effect of the fibrous membrane.
    Micro & Nano Letters 12/2014; 9(12):901-905. DOI:10.1049/mnl.2014.0447 · 0.85 Impact Factor
  • Source
    • "To avoid SCS current intensities that could be experienced as uncomfortable, before each stimulation session the intensity of each stimulation frequency was adjusted and set to 1.7 times the minimum intensity at which any behavioral response could be consistently detected (small postural changes, head or neck movements). Overall, as previously reported in rodents (Fuentes et al., 2009), we observed that SCS induced a clear alleviation of motor impairment in monkeys who exhibited severe clinical PD signs. Because the stimulation frequencies used in this study (range, 4–300 Hz) proved equally effective, the analysis of the SCS effects, both behavioral and electrophysiological, were performed by pooling all the frequencies, unless otherwise stated. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Although deep brain electrical stimulation can alleviate the motor symptoms of Parkinson disease (PD), just a small fraction of patients with PD can take advantage of this procedure due to its invasive nature. A significantly less invasive method — epidural spinal cord stimulation (SCS) — has been suggested as an alternative approach for symptomatic treatment of PD. However, the mechanisms underlying motor improvements through SCS are unknown. Here, we show that SCS reproducibly alleviates motor deficits in a primate model of PD. Simultaneous neuronal recordings from multiple structures of the cortico-basal ganglia-thalamic loop in parkinsonian monkeys revealed abnormal highly synchronized neuronal activity within each of these structures and excessive functional coupling among them. SCS disrupted this pathological circuit behavior in a manner that mimics the effects caused by pharmacological dopamine replacement therapy or deep brain stimulation. These results suggest that SCS should be considered as an additional treatment option for patients with PD.
    Neuron 11/2014; 84(4). DOI:10.1016/j.neuron.2014.08.061 · 15.05 Impact Factor
  • Source
    • "On the other hand, according to our electrical stimulation experiments on cerebral infarction model of rats, we had reported that low frequency stimulation (i.e. 2 or 10 Hz) were effective for reduction of volume of cerebral infarction [12]. Furthermore, 333 Hz SCS are used in the report of the effect of SCS for PD model [2]. Referring to these reports, we had selected these three stimulation frequencies (i.e. 2, 50, and 200 Hz). "
    [Show abstract] [Hide abstract]
    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.
    PLoS ONE 07/2014; 9(7):e101468. DOI:10.1371/journal.pone.0101468 · 3.23 Impact Factor
Show more