Breathing returns to paralyzed rats

WASHINGTON — Paralyzed rats can breathe a sigh of relief: A new treatment can restore lung function, even a year and a half after a spinal cord injury that takes it away.

When researchers injected a scar tissue–chewing enzyme into the rats’ spinal cords and then dialed down the animals’ oxygen intake, they could breathe easily again, neuroscientist Philippa Warren reported November 17 at the annual meeting of the Society for Neuroscience.

Warren and colleagues are the first to show that respiratory recovery is possible long after a paralyzing injury. For people on respirators, “Even minor improvements in the ability to breathe would be huge,” said neuroscientist Oswald Steward of the University of California, Irvine. Just being able to cough and clear one’s throat could help people recover from respiratory infections that might otherwise be fatal.

Damage to the spinal cord can kill people’s mobility, but taking their breath away is even worse, said Steward. Spinal cord injuries that hit high in the neck can freeze chest muscles that help people breathe. Normally, the brain tells the body to inhale via nerves that stretch to the diaphragm. This tough muscle lies beneath the lungs like a rubber sheet, flexing and relaxing to pull and push air into and out of the body. When an injury severs nerves in the spinal cord, the diaphragm goes limp.

Though there’s still no way to fix breathing ability in people with this type of paralysis, scientists have had some success in rats — but only if the rats receive treatment soon after a spinal cord injury. Chronic injury is a whole different ball game, Warren said. Over time, scar tissue stacks up, clogging the injury site with gummy fibers that stop new nerves from sprouting.

“The scar tissue never goes away, which means nothing can recover,” she said.

To test a new treatment for chronic injury, Warren first sliced halfway through rats’ upper spinal cords, paralyzing just one side of the diaphragm. With half the muscle pumping and half slumping, the animals could still breathe, but they had trouble coping with exercise or changes in oxygen levels.

Building on a technique developed by her colleagues at Case Western Reserve University in Cleveland, Warren injected an enzyme called chondroitinase ABC into the rats’ spinal cords to clear out scar tissue clutter a year and a half after their injury. Then she added a new twist, placing the rats in a low-oxygen chamber 10 times a day for five minutes. The oxygen cutback forced the animals to breathe deeper and faster, as if they lived at a high altitude, Warren said.

Three weeks of this lung workout combined with the single enzyme injection had two-thirds of injured rats breathing like healthy ones, Warren reported. She thinks coupling scar tissue–busting treatments with rehabilitation therapy could be the key to restoring breathing ability in paralyzed people, even well after the injury.

Other researchers are also working with the enzyme in hopes of testing it in humans.