Sympathetic Preganglionic Neurons (SPNs): a Promising Target to Regain Cardiorespiratory Control in Spinal Cord Injured (SCI) Patients

Abstract

BackgroundThe consequences of spinal cord injuries (SCI) are massive and become more severe with higher levels of injury. Lesions located on cervical portions, specifically between C1‐C3 cause an interruption of the descending bulbospinal pathways. These pathways include a key component of the neural control of respiration, linking the brainstem breathing rhythm generator with phrenic motor neurons that activate the diaphragm. Disruption to these pathways result in respiratory muscle paresis and/or paralysis, requiring mechanical ventilation. Respiratory complications, such as pneumonia and atelectasis complicate the process of weaning patients from ventilators, contributing to patient mortality. Previous data collected in the Wilson lab demonstrated that sympathetic preganglionic neurons (SPNs) located at the thoracic spinal cord have remarkable oxygen and pressure‐sensitive capabilities. Here, we hypothesized that SPNs can stimulate phrenic motor neurons independent of the brainstem.AimTo study the novel direct influence of SPNs on the phrenic motor nucleus.MethodsAn in situ artificially‐perfused cervico‐thoracic rat spinal cord preparation was used to record phrenic and splanchnic nerve activity while having the cervical and thoracic spinal cord separately perfused. This approach allowed us to selectively expose the thoracic segment to acute hypoxia (30 Torr; 10 min) in order to observe if cardiorespiratory responses elicited by the SPN’s could stimulate phrenic motor neurons located at the cervical spinal cord. Additionally, we recorded the electromyography activity from the diaphragm during hypoxia and ischemia (0 mmHg; 10 min).ResultsThe results demonstrated that stimulation of the SPNs with hypoxia evoked phrenic nerve and diaphragm activity. This indicates that even without inputs from the brainstem, SPNs are responsive to hypoxia and ischemia and might have capability to stimulate phrenic motor neurons.ConclusionThe implications of these findings point to the thoracic SPNs as a unique and promising target to regain cardiorespiratory control in SCI patients. Further pharmacological investigations may reveal effective treatment strategies to improve life quality and reduce mortality of SCI patients.Support or Funding InformationAlberta Innovates Health Solutions (LL), Eyes High (NB), NSERC (HY), Canadian Institute of Health Research (RW).