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Project

Cervical Spinal Epidural Stimulation and Respiratory Recovery After SCI

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
Epidural stimulation has the capacity to restore a variety of motor, sensory, and autonomic functions in both experimental and clinical conditions after spinal cord injury (SCI). Though limited underlying mechanisms have been proposed, to date little is known how epidural stimulation elicits motor function at the neuronal or neural circuit level. Even less is known about the capacity for epidural stimulation to promote long-lasting spinal plasticity for true device-independence. Accordingly, this Pilot Study will capitalize on the PI's long-term research interest in neurotherapeutic approaches for promoting plasticity and repair in the injured spinal cord via exploration of closed-loop epidural stimulation and neurotrophic factor expression and release. The central hypothesis is that transition from device-dependent short-term effects from closed-loop epidural stimulation to long-term, spinal plasticity requires facilitation of synaptic efficacy and possible remodeling of spinal circuitry facilitated by induced expression of neurotrophic factors. This proposal will focus on spinal inspiratory circuits after upper cervical spinal cord injury. These networks have been extensively characterized and, thus, serve to provide a more direct, multi-disciplinary interrogation of a simple motor circuit. Aim 1 will be a longitudinal study to determine if long-term closed-loop epidural stimulation leads to functional improvements beyond the period of stimulation in inspiratory motor output after high cervical SCI. Aim 2 will test the hypothesis that long-term cervical epidural stimulation will promote functional improvements via amplification of neurotrophic factor expression and possible circuit remodeling in inspiratory motor circuits. Preliminary data are promising and indicate at least some short-term plasticity with short periods of stimulation. We envision that more chronic and targeted stimulation parameters will result in longer persistence of motor recovery. This is the first study to propose chronic epidural stimulation in awake, freely-behaving animals in a defined respiratory neural circuit. Ultimately, data from this pilot project will serve to inform development of future investigations of the mechanistic basis of epidural stimulation efficacy essential for advancing the therapeutic applications to many motor systems. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1109 Neurosciences

  • RCDC

    Assistive Technology

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Bioengineering

  • RCDC

    Neurosciences

  • RCDC

    Rehabilitation

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • HRCS HC

    Neurological

  • HRCS RAC

    1.1 Normal biological development and functioning

  • Health Research Areas

    Biomedical