4.4 Review

Electrical epidural stimulation of the cervical spinal cord: implications for spinal respiratory neuroplasticity after spinal cord injury

Journal

JOURNAL OF NEUROPHYSIOLOGY
Volume 126, Issue 2, Pages 607-626

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/jn.00625.2020

Keywords

electrochemical analysis; epidural stimulation; respiratory neuroplasticity; spinal cord injury

Funding

  1. University of Florida McKnight Brain Institute
  2. University of Florida Brain and Spinal Cord Injury Research Trust Bridge Funds
  3. Craig H. Neilsen Foundation
  4. National Institutes of Health [OT2 OD-023854]
  5. Florida Department of Health Brain and Spinal Cord Injury Research Trust
  6. BREATHE Training Program [T32 HL-134621]
  7. University of Florida Graduate Student Preeminence Award

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This article details the development and success of electrical epidural stimulation (EES) in recovering locomotor function, as well as exploring its potential in other systems. While there has been some success in using EES for locomotor function recovery, its effectiveness in improving breathing function after cSCI remains limited.
Traumatic cervical spinal cord injury (cSCI) can lead to damage of bulbospinal pathways to the respiratory motor nuclei and consequent life-threatening respiratory insufficiency due to respiratory muscle paralysis/paresis. Reports of electrical epidural stimulation (EES) of the lumbosacral spinal cord to enable locomotor function after SCI are encouraging, with some evidence of facilitating neural plasticity. Here, we detail the development and success of EES in recovering locomotor function, with consideration of stimulation parameters and safety measures to develop effective EES protocols. EES is just beginning to be applied in other motor, sensory, and autonomic systems; however, there has only been moderate success in preclinical studies aimed at improving breathing function after cSCI. Thus, we explore the rationale for applying EES to the cervical spinal cord, targeting the phrenic motor nucleus for the restoration of breathing. We also suggest cellular/molecular mechanisms by which EES may induce respiratory plasticity, including a brief examination of sex-related differences in these mechanisms. Finally, we suggest that more attention be paid to the effects of specific electrical parameters that have been used in the development of EES protocols and how that can impact the safety and efficacy for those receiving this therapy. Ultimately, we aim to inform readers about the potential benefits of EES in the phrenic motor system and encourage future studies in this area.

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