By Allan Mai ‘20

After a traumatic spinal cord injury, a primary cause for concern is the threat of a dysfunctional respiratory system; a means by which to preserve respiratory functions is needed to decrease mortality rates in patients with spinal cord injuries. In a recent study, Dr. Kajana Satkunendrarajah of the Kembril Research Institute in Toronto discovered a potential solution to this problem which involves excitation of interneurons in the mid-cervical region of the spinal cord.

Using a rodent model, Dr. Satkunendrarajah and his team sought to demonstrate that respiratory function is preserved mainly through the recruitment of a subpopulation of neurons known as cervical excitatory interneurons (eINs). A non-traumatic spinal cord injury (ntSCI) was induced in a rat in which eINs had been silenced with a ligand known as PSEM, which effectively reduces neuronal activity when it binds to a receptor known as PSAM. The results from this procedure showed that inspiratory amplitude – the maximum amount of air that can be inhaled or exhaled – decreased by 33 percent. In addition, there was an increased number of cases of hypopnea in these rats, which led to short periods of low inspiratory activity. However, administering PSEM to the control rats had no effect on the rats’ respiration, which suggests that eINs are crucial for sustaining respiratory function in rats with spinal cord injuries but not in their uninjured counterparts.

Once the researchers had identified eINs as crucial to respiratory function in injured rats, they sought to develop methods to stimulate these neurons. In this part of the study, Satkunendrarajah and his colleagues showed that prompt excitation of the eINs after a spine injury is crucial to restoring respiratory function. They performed a C2 hemisection (an incision along the longitudinal plane) on a rat, then immediately stimulated the mid-cervical region of the spinal cordby administering eINs. Prompt stimulation led the left hemi-diaphragm of the rat improved to almost half its original amplitude and area; the activity of the left hemi-diaphragm was also synchronous with the uninjured side. In contrast, the SCI mice with no stimulation showed no signs of diaphragm activity on the injured side of the hemisection. Dr. Satkunendrarajah and his team are hoping that the implications of their study will translate to the clinical setting.

References

1. K. Satkunendrarajah, et. al., Cervical excitatory neurons sustain breathing after spinal cord injury. Nature (2018). doi: https://doi.org/10.1038/s41586-018-0595-z  
2. Image retrieved from: https://unsplash.com/photos/CKxD_Qh6ULY