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A flexible electrode array for determining regions of motor function activated by epidural spinal cord stimulation in rats with spinal cord injury.

ABSTRACT: Epidural stimulation of the spinal cord is a promising technique for the recovery of motor function after spinal cord injury. The key challenges within the reconstruction of motor function for paralyzed limbs are the precise control of sites and parameters of stimulation. To activate lower-limb muscles precisely by epidural spinal cord stimulation, we proposed a high-density, flexible electrode array. We determined the regions of motor function that were activated upon epidural stimulation of the spinal cord in a rat model with complete spinal cord, which was established by a transection method. For evaluating the effect of stimulation, the evoked potentials were recorded from bilateral lower-limb muscles, including the vastus lateralis, semitendinosus, tibialis anterior, and medial gastrocnemius. To determine the appropriate stimulation sites and parameters of the lower muscles, the stimulation characteristics were studied within the regions in which motor function was activated upon spinal cord stimulation. In the vastus lateralis and medial gastrocnemius, these regions were symmetrically located at the lateral site of L1 and the medial site of L2 vertebrae segment, respectively. The tibialis anterior and semitendinosus only responded to stimulation simultaneously with other muscles. The minimum and maximum stimulation threshold currents of the vastus lateralis were higher than those of the medial gastrocnemius. Our results demonstrate the ability to identify specific stimulation sites of lower muscles using a high-density and flexible array. They also provide a reference for selecting the appropriate conditions for implantable stimulation for animal models of spinal cord injury. This study was approved by the Animal Research Committee of Southeast University, China (approval No. 20190720001) on July 20, 2019.

SUBMITTER: Mao GW

PROVIDER: S-EPMC8504402 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundStimulation 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.MethodsWe 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.ResultsIn 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.ConclusionsTherefore 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.

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A flexible electrode array for determining regions of motor function activated by epidural spinal cord stimulation in rats with spinal cord injury.

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