☆ 4.5 Article

Closed-Loop, Cervical, Epidural Stimulation Elicits Respiratory Neuroplasticity after Spinal Cord Injury in Freely Behaving Rats

ENEURO (2022)

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ENEURO

卷 9, 期 1, 页码 -

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SOC NEUROSCIENCE

DOI: 10.1523/ENEURO.0426-21.2021

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cervical spinal cord injury; diaphragm EMG; epidural stimulation; respiratory neuroplasticity; respiratory rehabilitation; spinal motor evoked potentials

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Neurosciences

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More than half of spinal cord injuries are cervical, leading to paralysis and respiratory compromise. Existing treatments for restoring breathing after severe cervical injuries are lacking. Closed-loop stimulation triggered by healthy muscle activity has the potential to promote neuroplasticity in the respiratory pathways of the spinal cord.

Over half of all spinal cord injuries (SCIs) are cervical, which can lead to paralysis and respiratory compromise, causing significant morbidity and mortality. Effective treatments to restore breathing after severe upper cervical injury are lacking; thus, it is imperative to develop therapies to address this. Epidural stimulation has successfully restored motor function after SCI for stepping, standing, reaching, grasping, and postural control. We hypothesized that closed-loop stimulation triggered via healthy hemidiaphragm EMG activity has the potential to elicit functional neuro-plasticity in spinal respiratory pathways after cervical SCI (cSCI). To test this, we delivered closed-loop, electrical, epidural stimulation (CLES) at the level of the phrenic motor nucleus (C4) for 3 d after C2 hemisection (C2HS) in freely behaving rats. A 2 x 2 Latin Square experimental design incorporated two treatments, C2HS injury and CLES therapy resulting in four groups of adult, female Sprague Dawley rats: C2HS 1 CLES (n = 8), C2HS (n = 6), intact 1 CLES (n = 6), intact (n = 6). In stimulated groups, CLES was delivered for 12-20 h/d for 3 d. After C2HS, 3 d of CLES robustly facilitated the slope of stimulus-response curves of ipsilesional spinal motor evoked potentials (sMEPs) versus nonstimulated controls. To our knowledge, this is the first demonstration of CLES eliciting respiratory neuroplasticity after C2HS in freely behaving animals. These findings suggest CLES as a promising future therapy to address respiratory deficiency associated with cSCI.

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Respiratory Training and Plasticity After Cervical Spinal Cord Injury

Margo Randelman, Lyandysha V. Zholudeva, Stephane Vinit, Michael A. Lane

Summary: This article reviews the anatomical incompleteness and neuroplasticity resulting from spinal cord injuries, as well as how non-invasive respiratory treatments can enhance recovery. It focuses on current clinically used respiratory training strategies and those in development, while also considering the impact of training on non-respiratory networks. Insights are given on advances in pre-clinical and translational research in this area, with a look into future directions for enhancing plasticity and improving functional outcomes after SCI.

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