Closed-loop cervical epidural stimulation partially restores ipsilesional diaphragm EMG after acute C2 hemisection

Cervical spinal cord injury creates lasting respiratory deficits which can require mechanical ventilation longterm. We have shown that closed-loop epidural stimulation (CL-ES) elicits respiratory plasticity in the form of increased phrenic network excitability (Malone et. al., E Neuro, Vol 9, 0426-21.2021, 2022); however, the ability of this treatment to create functional benefits for breathing function per se after injury has not been demonstrated. Here, we demonstrate in C2 hemisected anesthetized rats, a 20-minute bout of CL-ES administered at current amplitudes below the motor threshold restores paralyzed hemidiaphragm activity in-phase with breathing while potentiating contralesional activity. While this acute bout of stimulation did not elicit the increased network excitability seen in our chronic model, a subset of stimulated animals continued spontaneous ipsilesional diaphragm activity for several seconds after stopping stimulation. These results support the use of CL ES as a therapeutic to rescue breathing after high cervical spinal cord injury, with the potential to lead to lasting recovery and device independence.

Automated summary

Closed-loop epidural stimulation (CL-ES) can improve respiratory deficits caused by cervical spinal cord injury, restoring diaphragm activity and enhancing contralateral activity. This treatment has the potential to lead to lasting recovery and device independence.