Abstract
Restoration of movement following spinal cord injury (SCI) has been achieved using electrical stimulation of peripheral nerves and skeletal muscles. However, practical limitations such as the rapid onset of muscle fatigue hinder clinical application of these technologies. Recently, direct stimulation of alpha motor neurons has shown promise for evoking graded, controlled, and sustained muscle contractions in rodent and feline animal models while overcoming some of these limitations. However, small animal models are not optimal for the development of clinical spinal stimulation techniques for functional restoration of movement. Furthermore, variance in surgical procedure, targeting, and electrode implantation techniques can compromise therapeutic outcomes and impede comparison of results across studies. Herein, we present a protocol and large animal model that allow standardized development, testing, and optimization of novel clinical strategies for restoring motor function following spinal cord injury. We tested this protocol using both epidural and intraspinal stimulation in a porcine model of spinal cord injury, but the protocol is suitable for the development of other novel therapeutic strategies. This protocol will help characterize spinal circuits vital for selective activation of motor neuron pools. In turn, this will expedite the development and validation of high-precision therapeutic targeting strategies and stimulation technologies for optimal restoration of motor function in humans.
Highlights
Limb movement is controlled by effector motor neurons and synaptic relays within the ventral horn grey matter of the spinal cord that receive inputs from higher brain centers
The time required for experimental testing depended upon the specific epidural or intraspinal stimulation protocol and can be safely extended under anesthesia
Traumatic injury to the spinal cord can result in permanent loss of motor, sensory, and autonomic function, significantly reducing quality of life for affected individuals
Summary
Limb movement is controlled by effector motor neurons and synaptic relays within the ventral horn grey matter of the spinal cord that receive inputs from higher brain centers. Multiple studies of intraspinal stimulation have been successful in safely evoking coordinated limb movement and weight-bearing while improving fatigue-resistance in small animal models of SCI [5,6,7,8,9]. Development of ISMS technology and functional stimulation paradigms for human application requires a model with appropriate dimensions and structure for accurate comparisons as well as evaluation of safety and efficacy. There is a clear need for a large animal model that closely resembles the neuroanatomy of the human spinal cord and allows the development of novel, effective, safe, and cost-effective therapeutic paradigms. The neuroanatomy of the porcine spinal cord closely resembles that of humans [20] and represents a low-cost alternative to nonhuman primate models for the development and application of ISMS technology
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