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Scientists bridge’ spinal injury nerve gap

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Like linemen stringing an electric cable over a gorge, a research team co-directed by a Cleveland scientist has devised a way to coax nerve fibers to grow a “bridge” across gaps in rats’ damaged spinal cords.

The new technique, reported today in the Journal of Neuroscience, successfully re-established some neural connections and restored a “considerable” amount of movement in five of seven partially paralyzed rats, according to the researchers.

After treatment, animals that had been dragging their forelimbs were able to plant their front feet, bear weight and bend their arms to touch their faces.

“I think it’s a real milestone,” said Case Western Reserve University neuroscientist Jerry Silver, who co-authored the study with neuroscientist John Houle of Philadelphia’s Drexel University. “It’s not walking and it’s not running. But it’s a start. It clearly shows [nerve] Regeneration can occur, and it can be Functional.”

“With this system we’ve just touched the surface of what we’re going to be able to do,” Houle said.

Silver and Houle intend to launch testing in several months to determine whether the technique works in monkeys, whose central nervous systems are more similar to humans’ in size and complexity. If that work is successful, human research could follow in several years.

While optimistic, both researchers caution that even if the bridging approach proves feasible in humans, it may not be able to restore all types of movement.

Different regions of the 2-foot-long human spinal cord control specific functions, so if an injury is in the neck, it might not be possible to regenerate nerve fibers long enough to reach the area low in the spine responsible for leg or foot movements.

However, even small gains could make a big difference to a paralyzed person, said Oswald Steward, director of the University of California’s Reeve-Irvine Research Center.

Breathing without need of a mechanical Ventilator would be a big advance, Steward said. So would regaining the ability to grasp a fork, or to move unaided from a bed to a wheelchair.

“Reanimating just that muscle could transform a person’s ability to live independently,” said Steward, who was not involved in the research. “It’s another reason this paper is so important.”

For decades, scientists have sought a way to repair spinal cord damage, which paralyzes more than 11,000 Americans each year.

The devastating injuries typically result from vehicle crashes, falls, sports accidents or gunshot wounds. Patients face hundreds of thousands of dollars in medical costs and lost income, as well as shortened lives due to infections or blood clots.

The spinal cord is a superhighway constantly ferrying messages between the brain and the body — simple, automatic ones, like how fast to breathe on a jog; and conscious, intricate ones such as when to swing at a fastball or how to play a piano concerto.

Those electro-chemical messages zip up and down the spinal cord, transmitted by strings of neurons, or nerve cells, that function as wiring. The cord is packed with millions of neurons. Each has a long, thin fiber dangling like a tail. This antenna, called an Axon, conveys signals from the Neuron to its closest neighbor.

If the cord is cut or crushed, individual axons are severed, breaking the link.

Injured axons can regrow, but the body throws up powerful obstacles. Within 24 hours, the damaged part of the cord is flooded with chemicals called proteoglycans. These slimy molecules are natural bandages. They form a seal to keep the wound from enlarging, but also somehow discourage regenerating axons from entering the site — possibly with a “keep out” signal.

Eventually, a tough, rubbery scar forms at the injury site. In combination, the scar and the proteoglycans are like guard dogs and an electrified fence. Regrowing axons edge close, then stop or turn away. The stalled nerve endings form blunt, angry bulbs that resemble clenched fists.

When confronted with a formidable barricade, the obvious solution is to circumvent it. But persuading axons to detour out of, then back into, the cord to get around the wound site isn’t easy.

In the comfy environs of the spinal cord, axons are the divas, surrounded by an entourage of servile cells whose job is to keep the spindly nerve fibers well-nourished, swaddled in insulation, physically supported and otherwise pampered. Outside the cord, it’s a hostile world. Why would they want to leave?

Since the early 1900s, researchers have experimented with using a Peripheral nerve segment from elsewhere in the body as a scaffold or bridge upon which spinal axons could grow around a scar. Crushing the peripheral nerve killed its own fibers, leaving behind a cast of servant cells revved up to support a new occupant.

Scientists found that axons would enter the bridge. But they refused to exit the other end and rejoin the spinal cord. The axons seemed to be “addicted” to their cushy new digs. No one could find a way to lure them out.

Meanwhile, Silver and other researchers had learned a lot about proteoglycans, the inhibitory guard dogs that scared axons away. If the molecules could be muzzled, would the skittish nerve fibers leave the bridge and complete their journey?

For help, Silver and Houle turned to a nasty bacteria with a nasty name, Proteus vulgaris. When it’s trying to invade, P. vulgaris attacks the body’s defense system. It spits out an enzyme, chondroitinase, that chews up proteoglycans — exactly the neutralizing effect the scientists were looking for.

Used selectively, chondroitinase might knock down the last barrier to splicing the spinal cord with a nerve bridge.

To test the idea under conditions that mimicked human spinal injuries, Houle surgically removed a slice of the cord in a group of lab rats. That paralyzed one of the rats’ two front legs. He also snipped out a piece of the sciatic nerve from the rats’ hind legs, to use as the bridge.

After crushing the nerve to kill its own fibers and ready it for new growth, Houle stitched one end to the cord. He left the other end unconnected.

Two weeks later — enough time for axons to enter the bridge — Houle installed a tiny pump lower down on the cord, at the site where the bridge’s loose end would be reattached.

In some rats, the pump delivered saline, which should have no effect.

Others got a five-day dose of chondroitinase, the enzyme that was supposed to pave the way for nerves to reconnect.

After the pumps were removed, the unfastened ends of the bridges were sewn in place. Then observers rated how well the rats were able to move. They reported significant differences between the treated and untreated animals.

When placed on a thick rope, three of the seven chondroiti nase-dosed rats were able to rise on their formerly paralyzed forelimbs and walk with difficulty. None of the five saline-treated rats stood up.

Five of the seven chondroitinase rats could bend their forelimbs more than 90 degrees, and three could touch their faces, although they couldn’t groom. The farthest the saline rats could flex was 90 degrees.

Though the results are impressive, Silver and Houle believe they can do better.

Even with chondroitinase clearing the path, less than 30 percent of the axons that entered the nerve bridge grew out the other end to reconnect with the rats’ spinal cords.

Treating both ends of bridge or delivering a bigger dose could boost nerve growth, improving mobility. So might using multiple bridges.

“As soon as possible we’re going to organize the primate studies,” said Silver, 59. “I’m not messing around. I want to do this in a human before I retire.”

To see videos comparing the movement of treated and untreated rats, go to

John Mangels
Plain Dealer Science Writer

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