Effect of spinal cord injury on the respiratory system: basic research and current clinical treatment options

Abstract

Spinal cord injury (SCI) often leads to an impairment of the respiratory system. The more rostral the level of injury, the more likely the injury will affect ventilation. In fact, respiratory insufficiency is the number one cause of mortality and morbidity after SCI. This review highlights the progress that has been made in basic and clinical research, while noting the gaps in our knowledge. Basic research has focused on a hemisection injury model to examine methods aimed at improving respiratory function after SCI, but contusion injury models have also been used. Increasing synaptic plasticity, strengthening spared axonal pathways, and the disinhibition of phrenic motor neurons all result in the activation of a latent respiratory motor pathway that restores function to a previously paralyzed hemidiaphragm in animal models. Human clinical studies have revealed that respiratory function is negatively impacted by SCI. Respiratory muscle training regimens may improve inspiratory function after SCI, but more thorough and carefully designed studies are needed to adequately address this issue. Phrenic nerve and diaphragm pacing are options available to wean patients from standard mechanical ventilation. The techniques aimed at improving respiratory function in humans with SCI have both pros and cons, but having more options available to the clinician allows for more individualized treatment, resulting in better patient care. Despite significant progress in both basic and clinical research, there is still a significant gap in our understanding of the effect of SCI on the respiratory system.

Figure 1. Schematic drawing of the major respiratory neural centers and pathways in the rat. Respiratory rhythm generation is formed by neurons located within the pFRG and the PBC. Impulses are transmitted to premotor neurons located within the VRG with inspiratory neurons located predominantly in rVRG and expiratory neurons localized to cVRG. Premotor neurons project either unilaterally or bilaterally down to phrenic motor neurons located on both sides of the spinal cord (C3–C6). Crossed respiratory axons (arising from VRG neurons bilaterally) have been localized at the level of the phrenic nucleus and contribute to the expression of the crossed phrenic phenomenon. Phrenic axons from each side of the spinal cord form the phrenic nerve, which projects to each half of the diaphragm.