CASE WESTERN (US) — Scientists restored breathing function in mice by bridging a spinal cord injury and regenerating lost nerve connections to the diaphragm.
More testing is necessary, but researchers are hopeful their technique will quickly be used in clinical trials.
Restoring breathing is the a top priority for people with upper spinal cord injuries, researchers say. Many rely on ventilators to breathe, which can be inconvenient and potentially dangerous.
“We use an old technology—a peripheral nerve graft—and a new technology—an enzyme—to restore breathing to nearly normal,” says Jerry Silver, professor of neurosciences at Case Western Reserve University and senior author of a study published in Nature.
Using a graft from the sciatic nerve, surgeons have been able to restore function to damaged peripheral nerves in the arms or legs for 100 years. But, they’ve had little or no success in using a graft on the spinal cord.
Nearly 20 years ago, Silver found that after a spinal injury, a structural component of cartilage, called chondroitin sulfate proteoglycans, was present and involved in the scarring that prevents axons from regenerating and reconnecting.
Silver knew that the bacteria Proteus vulgaris produced an enzyme called Chondroitinase ABC, which could break down such structures. In previous testing, he found that the enzyme clips the inhibitory sugary branches of proteoglycans, essentially opening routes for nerves to grow through.
In the new study, the researchers bridged a spinal cord injury at the second cervical level using a section of peripheral nerve and injected Chondroitinase ABC.
The enzyme promotes neuron growth and plasticity. Within the graft, Schwann cells, which provide structural support and protection to peripheral nerves, guide and support the long-distance regeneration of the severed spinal nerves.
Nearly 3,000 severed nerves entered the bridge and 400 to 500 nerves grew out the other side, near disconnected motor neurons that control the diaphragm. There, Chondrointinase ABC prevented scarring from blocking continued growth and reinnervation.
“All the nerves hook up with interneurons and somehow unwanted activities are filtered out but signals for breathing come through,” Silver says. “The spinal cord is smart.”
Three months after the procedure, tests recording nerve and muscle activity showed that 80 to more than 100 percent of breathing function was restored. Breathing function was maintained at the same levels six months after treatment.
Silver’s lab has already begun preliminary work to restore bladder function—the top request of people who suffer lower spinal cord injuries. He is unsure whether the technique would be useful in restoring something as complicated as walking, but for breathing or holding and expelling urine, the tests so far indicate the procedure works well.
How long after injury the nerves are still capable or regeneration and re-connection, he doesn’t know. But, Silver believes that more than the newly-injured could potentially benefit from the procedure.
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