Targeting Respiratory Neuroplasticity Following Cervical Spinal Cord Injury: Perspective from Experiment to Clinic

Cervical spinal cord injuries (CSCIs) can cause permanent functional impairments such as respiratory dysfunction. In such cases, patients usually require ventilatory assistance to survive, and even those with the ability to wean from the device still suffer life-threatening deficits. In order to maintain and/or restore voluntary breathing control following a high-level SCI, phrenic motor neuron activity must be preserved and/or restored. The current treatment for CSCI does not provide complete restoration of respiratory circuits and recovery of diaphragm function and activity, making it clinically important to study. At the bench, various strategies, including pharmacological interventions, electrical stimulation, and activity-based therapies, are being explored to harness neuroplasticity in the central nervous system for respiratory recovery after CSCI. Multiple animal models have provided preclinical evidence for respiratory plasticity, laying the foundation for clinical translation. Although extensive research on this injury has been conducted in experimental models, relatively few treatments have progressed to the clinic. In this review, we highlight (1) the anatomical and physiological changes in respiratory pathways after CSCI, (2) describe the current progress in the regeneration of phrenic circuits after CSCI, and provide an overview of therapeutic strategies aimed at restoring respiratory function. We will also (3) discuss the effectiveness of auxiliary treatment approaches and how scientists can shift these means from bench to clinical research.