New neural network restores diaphragm function after spinal cord injury

Many patients with spinal cord injuries must rely on a ventilator to breathe due to paralysis of the diaphragm.
By Amy Wallace  |  Oct. 20, 2017 at 2:16 PM
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Oct. 20 (UPI) -- Researchers at Case Western Reserve University School of Medicine have made a discovery that may revolutionize the treatment of spinal cord injuries.

Individuals who experience spinal cord injuries are often reliant on a ventilator due to the fact that the diaphragm becomes paralyzed as in quadriplegia.

The researchers at CWR found that two different sets of neural signals control the movement of the diaphragm in rats and mice -- one neural pathway originates in the brain, and the other in the spinal cord.

The study, published in the October edition of Cell Reports, used a drug to turn this alternative nerve pathway on and restore breath-like movements in rodents.

"We found a way to make the diaphragm work again in mice and hope the same approach could be applied to humans," Jared Cregg, a graduate student in the Neurosciences Department at Case Western Reserve University School of Medicine, told UPI.

"We discovered a new circuit in the spinal cord that nobody knew of before. We describe it functionally based on the types of neurons in the network. We induced cervical level injury in rats and mice. We induced paralysis on the left side and found that correlated to the diaphragm function on the left side. We applied drugs that block inhibitions which kind of released the brakes so the diaphragm could start moving again."

Spinal cord injury leads to paralysis in approximately 17,000 people in the U.S. each year. Many of those injured must rely on mechanical ventilators to breathe.

By discovering the new network, researchers could help spinal cord injury patients bypass missing brain signals and return motor function below injury sites -- reducing the need for ventilators.

Patients on ventilators for a long period of time are at an increased risk for developing serious, potentially fatal infections. Bacteria can grow in breathing tubes in the lungs, leading to pneumonia or septicemia.

Diaphragm muscle atrophy, which can develop from not using their diaphragm during long-term ventilator use, can reduce the chance of patients of ever breathing on their own.

According to the National Heart, Lung and Blood Institute, ventilator-associated pneumonia is a serious risk factor for patients on ventilators and other complications include risk for blood clots, serious skin infections, pneumothorax, lung damage and oxygen toxicity.

"It would benefit patients to be able to get them off the ventilator," Cregg said.

When researchers treated the rodents with inhibitor drugs, they were able to induce electricity that originated in the spinal cord, not the brain. The researchers then used optogenetics -- the use of light to "flip switches" inside neurons -- to induce electrical signals in the diaphragm.

The findings show the diaphragm can operate via nerve circuitry entirely separate from the brain.

"We have discovered a way to control the diaphragm in the absence of input from the brain. This exciting discovery may pave the way for future strategies aimed at augmenting motor output after cervical spinal cord injury," Cregg said.

Cregg cautions that the research is in the early stages and they have conducted acute experiments for short periods of time, but that longer term studies need to be done before expanding to human trials.

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