A new study takes lessons from a spinal osteoarthritic condition to identify a neural population that can be used to restore breathing after spinal cord injury. One of the most devastating features of high spinal cord injury is the disruption of the neural circuits that control breathing. Damage to these pathways frequently results in ventilator-dependence, pulmonary infections, and death.
Cervical spondylotic myelopathy (CSM) is a degenerative condition where arthritic changes in the spine slowly compress and damage the spinal cord. However, despite significant damage to the spinal cord regions associated with breathing, CSM patients don’t develop the devastating respiratory deficiency observed after spinal cord injury.
“The reason why these individuals don’t have respiratory issues despite substantial damage to the spinal cord was a complete mystery. It really pushed us to investigate what was responsible for this extraordinary preservation of respiratory function,”
said Dr Kajana Satkunendrarajah of the Krembil Research Institute, University Health Network, Toronto.
Cervical Excitatory Neurons
Using pre-clinical models of both CSM and spinal cord injury, the research team from the Krembil Research Institute and University of Toronto employed cutting-edge techniques to discover a group of spinal cord neurons that were vitally important to the maintenance of breathing once the respiratory neural network compromised.
“These neurons are not required for breathing under normal conditions. However, they become vital to the neural respiratory system when it is under challenge,”
said co-author Dr Spyridon Karadimas.
The researchers went on to use chemogenetic approaches, which utilize synthetic receptors to selectively activate or inactivate neurons, to demonstrate the function of this group of neurons after spinal cord injury. Using this “remote control” strategy, they found that manipulation of these neurons could reinstate breathing almost immediately after spinal cord injury.
“We think that this discovery has big implications for neuroscience in general, as it provides an important role for this neuronal population in the complex respiratory neural network,”
explained Dr Satkunendrarajah.
Funding for the study was provided by the Krembil Foundation, The Toronto General & Western Hospital Foundation, The Canadian Institutes of Health Research (CIHR), The Paralyzed Veterans Association (PVA), AOSpine North America, the Onassis Foundation and the Dezwirek Foundation.
Kajana Satkunendrarajah, Spyridon K. Karadimas, Alex M. Laliberte, Gaspard Montandon & Michael G. Fehlings
Cervical excitatory neurons sustain breathing after spinal cord injury
Nature 10 October 2018
Image: University of Huddersfield