Dataset Information

Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats.

ABSTRACT:

Background

Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array.

Methods

We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1-100 Hz and 1-10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats.

Results

In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia.

Conclusions

Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles.

SUBMITTER: Gad P

PROVIDER: S-EPMC3599040 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Publications

Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats.

Gad Parag P Choe Jaehoon J Nandra Mandheerej Singh MS Zhong Hui H Roy Roland R RR Tai Yu-Chong YC Edgerton V Reggie VR

Journal of neuroengineering and rehabilitation 20130121

<h4>Background</h4>Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has ...[more]

PMID: 23336733

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Project description:Background: Regaining control of movement following a spinal cord injury (SCI) requires utilization and/or functional reorganization of residual descending, and likely ascending, supraspinal sensorimotor pathways, which may be facilitated via task-specific training through body weight supported treadmill (BWST) training. Recently, epidural electrical stimulation (ES) combined with task-specific training demonstrated independence of standing and stepping functions in individuals with clinically complete SCI. The restoration of these functions may be dependent upon variables such as manipulation of proprioceptive input, ES parameter adjustments, and participant intent during step training. However, the impact of each variable on the degree of independence achieved during BWST stepping remains unknown. Objective: To describe the effects of descending intentional commands and proprioceptive inputs, specifically body weight support (BWS), on lower extremity motor activity and vertical ground reaction forces (vGRF) during ES-enabled BWST stepping in humans with chronic sensorimotor complete SCI. Furthermore, we describe perceived changes in the level of assistance provided by clinicians when intent and BWS are modified. Methods: Two individuals with chronic, mid thoracic, clinically complete SCI, enrolled in an IRB and FDA (IDE G150167) approved clinical trial. A 16-contact electrode array was implanted in the epidural space between the T11-L1 vertebral regions. Lower extremity motor output and vertical ground reaction forces were obtained during clinician-assisted ES-enabled treadmill stepping with BWS. Consecutive steps were achieved during various experimentally-controlled conditions, including intentional participation and varied BWS (60% and 20%) while ES parameters remain unchanged. Results: During ES-enabled BWST stepping, the knee extensors exhibited an increase in motor activation during trials in which stepping was passive compared to active or during trials in which 60% BWS was provided compared to 20% BWS. As a result of this increased motor activation, perceived clinician assistance increased during the transition from stance to swing. Intentional participation and 20% BWS resulted in timely and purposeful activation of the lower extremities muscles, which improved independence and decreased clinician assistance. Conclusion: Maximizing participant intention and optimizing proprioceptive inputs through BWS during ES-enabled BWST stepping may facilitate greater independence during BWST stepping for individuals with clinically complete SCI. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02592668.

Project description:Epidural electrical stimulation can restore limb motor function after spinal cord injury by reactivating the surviving neural circuits. In previous epidural electrical stimulation studies, single electrode sites and continuous tetanic stimulation have often been used. With this stimulation, the body is prone to declines in tolerance and locomotion coordination. In the present study, rat models of complete spinal cord injury were established by vertically cutting the spinal cord at the T8 level to eliminate disturbance from residual nerve fibers, and were then subjected to epidural electrical stimulation. The flexible extradural electrode had good anatomical topology and matched the shape of the spinal canal of the implanted segment. Simultaneously, the electrode stimulation site was able to be accurately applied to the L2-3 and S1 segments of the spinal cord. To evaluate the biocompatibility of the implanted epidural electrical stimulation electrodes, GFAP/Iba-1 double-labeled immunofluorescence staining was performed on the spinal cord below the electrodes at 7 days after the electrode implantation. Immunofluorescence results revealed no significant differences in the numbers or morphologies of microglia and astrocytes in the spinal cord after electrode implantation, and there was no activated Iba-1+ cell aggregation, indicating that the implant did not cause an inflammatory response in the spinal cord. Rat gait analysis showed that, at 3 days after surgery, gait became coordinated in rats with spinal cord injury under burst stimulation. The regained locomotion could clearly distinguish the support phase and the swing phase and dynamically adjust with the frequency of stimulus distribution. To evaluate the matching degree between the flexible epidural electrode (including three stimulation contacts), vertebral morphology, and the level of the epidural site of the stimulation electrode, micro-CT was used to scan the thoracolumbar vertebrae of rats before and after electrode implantation. Based on the experimental results of gait recovery using three-site stimulation electrodes at L2-3 and S1 combined with burst stimulation in a rat model of spinal cord injury, epidural electrical stimulation is a promising protocol that needs to be further explored. This study was approved by the Animal Ethics Committee of Chinese PLA General Hospital (approval No. 2019-X15-39) on April 19, 2019.

Dataset Information

Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats.

Background

Methods

Results

Conclusions

Publications

Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats.

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