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

ENEURO, 2022 · DOI: https://doi.org/10.1523/ENEURO.0426-21.2021 · Published: January 20, 2022

Spinal Cord Injury Pulmonology Neurology

Simple Explanation

Spinal cord injuries, especially in the neck area, can severely impact breathing. This study explores a new method using electrical stimulation to improve breathing after such injuries. The method involves stimulating the spinal cord in rhythm with the rat's breathing. Rats with spinal cord injuries received electrical stimulation timed with their breathing. The stimulation was delivered through electrodes placed on the spinal cord in the neck. The goal was to see if this stimulation could help the rats' breathing muscles work better after the injury. The results showed that this type of stimulation improved the rats' ability to activate their breathing muscles. This suggests that the method could be a promising way to help people with spinal cord injuries breathe more easily.

Study Duration

3 d of CLES, measurements for 4 d after

Participants

Adult, female Sprague Dawley rats: C2HS + CLES (n=8), C2HS (n=6), intact + CLES (n=6), intact (n=6)

Evidence Level

Not specified

Key Findings

1
CLES robustly facilitated the slope of stimulus-response curves of ipsilesional spinal motor evoked potentials (sMEPs) versus nonstimulated controls after C2HS.
2
Motor threshold was significantly lower in rats that received CLES compared with rats that did not receive CLES, suggesting increased excitability of the phrenic motor network.
3
In C2HS + CLES rats, ipsilesional peak-to-peak amplitude was significantly larger in the 9- to 13-ms time bin on day 3 compared with day 0, suggesting recruitment of polysynaptic pathways.

Research Summary

This study investigated the potential of closed-loop epidural stimulation (CLES) to elicit respiratory neuroplasticity after cervical spinal cord injury (cSCI) in freely behaving rats. The results demonstrated that CLES, delivered at the level of the phrenic motor nucleus (C4) for 3 days after C2 hemisection (C2HS), facilitated the slope of stimulus-response curves of ipsilesional spinal motor evoked potentials (sMEPs). The findings suggest that CLES is a promising therapy to address respiratory deficiency associated with cSCI and warrants further investigation.

Practical Implications

Potential Therapeutic Strategy

CLES could be developed as a neuromodulatory strategy to restore breathing function in individuals with severe cSCI.

Improved Quality of Life

The therapy may improve the quality of life for individuals dependent on mechanical ventilation for survival.

Future Research Directions

Further studies are needed to explore the mechanisms underlying CLES-induced neuroplasticity and to validate its rehabilitative potential in chronic SCI models.

Study Limitations

1
More evidence is needed to assert CLES as a rehabilitative respiratory therapy.
2
Testing the rehabilitative potential of CLES will likely require both longer timepoints postinjury and ultimately need to be repeated and validated in rats with chronic SCI.
3
The closed-loop nature of the paradigm itself may be beneficial, but has not been directly tested.

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