Treatments to restore respiratory function after spinal cord injury and their implications for regeneration, plasticity and adaptation

Abstract

Spinal cord injury (SCI) often leads to impaired breathing. In most cases, such severe respiratory complications lead to morbidity and death. However, in the last few years there has been extensive work examining ways to restore this vital function after experimental spinal cord injury. In addition to finding strategies to rescue breathing activity, many of these experiments have also yielded a great deal of information about the innate plasticity and capacity for adaptation in the respiratory system and its associated circuitry in the spinal cord. This review article will highlight experimental SCI resulting in compromised breathing, the various methods of restoring function after such injury, and some recent findings from our own laboratory. Additionally, it will discuss findings about motor and CNS respiratory plasticity and adaptation with potential clinical and translational implications.

Figure 1. A schematic of the medullary-spinal cord respiratory circuitry

From the brainstem, bilateral projections are made from the RVRG (green) to the phrenic nucleus (red), providing the inspiratory drive. These pathways decussate at the medulla, as well as at the cervical spinal cord, which comprises the crossed phrenic pathway and is normally latent. Following injury at the cervical level, these pathways become interrupted resulting in impaired diaphragm activity. Furthermore, these bulbospinal projections are not exclusively monosynaptic, with interneurons dispersed in the circuitry (blue). These interneurons have become a target to restore function after injury.