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Paralyzed rats relearn to pee

Bladder control restored for the first time in animals with stark spinal cord damage

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Paralyzed rats can now decide for themselves when it’s time to take a leak. Animals in a new study regained bladder control thanks to a new treatment that coaxes severed nerves to grow.

Instead of dribbling out urine, the rodents squeezed out shots of pee almost as well as healthy rats do, researchers report June 25 in the Journal of Neuroscience. The study is the first to regenerate nerves that restore bladder function in animals with severely injured spinal cords.

“This is a very big deal,” says neurologist John McDonald of the Kennedy Krieger Institute in Baltimore, Md. If the treatment works in people with spinal cord injuries, he says, “it would change their lives.”

Unlike paralyzed rats, severely paralyzed humans can’t leak urine to relieve a full bladder. Unless injured people are fitted with a catheter, urine backs up into the kidneys. “These people get kidney failure all the time,” says study leader Jerry Silver, a neuroscientist at Case Western Reserve University in Cleveland. “It’s a terrible problem. If they didn’t have the catheter, they would die.”

Some of the worst spinal cord injuries sever the bundle of nerve cells that reach from a mammal’s brain down through the vertebrae. The neurons can’t just grow back. Instead, the cells’ stumps get stuck in a gummy thicket of scar tissue that forms around the wound.

Silver’s team has spent years refining a technique to tear down scar tissue and encourage damaged nerve cells to grow. The researchers snip out a healthy nerve bundle from between rats’ ribs, graft it onto a damaged section of spinal cord and then add an enzyme that chews up scar tissue. In 2006, his team used the technique to return some limb control to rats with one paralyzed forepaw. And in 2011, they helped paralyzed rats regain the ability to breathe.

In both cases, the rats retained bladder control after their injury because researchers had snipped only halfway through the bundle of spinal cord nerves. For the new study, the researchers chopped out a hunk of the rats’ spinal cords, severing the entire nerve bundle and leaving a gap about the width of a pencil. They then pumped up the treatment protocol from the earlier studies by adding a growth factor to the injury site.

Over several months, the damaged nerves slowly regenerated. They inched down through the grafted nerves, and then, says Silver, “they kept going and going like little Energizer bunnies.” After six months, the rats could mostly control their bladders and could even wiggle their legs a bit.

The new method may have potential beyond restoring bladder control. It could also restore sensation to the skin, which could help paralyzed people detect and avoid bedsores, says neuroscientist Lars Olson of the Karolinska Institute in Stockholm. “This is one of the most important steps that I have seen in recent years,” he says.

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