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Paralyzed Mice Able to Regain Movement, Study Reveals

BY Admin  January 17, 2008 at 3:30 PM EDT

mouse

The mouse’s brain and spinal cord can, when left to their own devices, sometimes bypass an injured area, creating a series of detours to find their own way to send the necessary messages from the brain to limbs to allow movement again, according to a new study.

“This is perhaps the most exciting thing I’ve ever worked on. And I’ve been at this for 30 years,” says Michael Sofroniew, a University of California, Los Angeles neurobiologist and the lead researcher on the study, which was published last week in Nature Medicine.

He cautions, however, that the work in mice, while exciting, is still a long way from providing a cure for human spinal cord injuries.

It’s not new to scientists that the brain has the ability to change its structure to cope with the environment. In fact, the brain is continually growing, pruning and rewiring its connections as we develop and learn new skills.

But until now, the prevailing belief has been that treating a spinal cord injury requires repairing the original nerves, which carry the signals sent from the brain to the body. The fact that the brain’s plasticity extends to the spinal cord is novel, and may hold clues for rehabilitation and treatment for some spinal injuries.

The spinal cord, a long, thick cluster of nerve tissue that extends from the brain to the base of the spine, contains portions of the longest nerve cells in the body. These nerve cells have stringy branches called axons, which are pathways the brain uses to send messages to the body. It is believed that the long nerve cells — called supraspinal nerves — originate in the brain and connect to a complex system of shorter nerves — propriospinal nerves — in the lower lumbar region of the spine. These short nerves connect to another short nerve fiber, which connects to the muscles that allow you to cross your legs or kick a soccer ball.

This nerve circuit controls walking. When the nerves are severed, the messages are disrupted, and the ability to walk is lost. A hard hit to the spine can lead to a devastating injury.

As many as 11,000 people suffer spinal cord injuries every year and nearly 300,000 people in the United States are living with spinal cord injuries, according to the National Spinal Cord Injury Statistical Center.

The question, Sofroniew said, was whether the long nerves needed to be repaired after an injury or whether other nerves could reorganize to take on their duties.

“There’s been a groundswell in other areas like stroke that the brain can make at least small adaptations. And we are continually surprised by its ability to do so,” he said.

In their experiment, the scientists severed the long supraspinal nerve of one side of a mouse’s spine, paralyzing one hind leg. Ten weeks later, they severed the nerve on the other side of the spine in a different spot, paralyzing the second hind leg. The injury meant that the brain was no longer able to send messages through these long fibers, and the cuts resulted in paralysis.

But over time, both limbs recovered. As time passed, the mice began to exhibit what Sofroniew called “discoordinated movement.” Walking involves alternating different sets of muscles, or contracting certain muscles while others relax. But at first the mice were trying to use all of the muscles at once. Over time, they became more coordinated until finally they were able to walk again. Their movement was less efficient than it had been before the injury, but they were walking.

The researchers suspected that the brain had rerouted messages to the spinal cord via the shorter propriospinal fibers. When the scientists injected chemicals into the short propriospinal nerves, the paralysis returned, confirming their hypothesis. The short nerves were compensating for the long ones. They were crucial to the recovery.

Sofroniew uses a freeway analogy to explain the process. “If you can’t get through on the freeway, you get off and drive through a series of surface streets. It’s less efficient, it takes longer and it doesn’t work quite as well, but you can get through.”

Reggie Edgerton, professor of neurobiology and physiology at UCLA and a co-author of the study, said he thinks the mice were exercising their brain well before they could move again. When they tried to move, the brain circuits that controlled movement were activated, and this strengthened the relevant pathways, allowing new connections to form.

“We think spontaneous recovery is in part due to routine practice occurring in the cage,” he said. “They were trying to walk, and the brain was already trying to reestablish connections due to intent.”

In other words, brain activity led to new cellular connections that, in turn, reprogrammed the brain and spinal cord. In this case, the brain and spinal cord were reprogrammed to learn how to walk again by using a different circuit of nerves.

“One should not generalize too far,” cautions James Guest, associate professor in neurological surgery at the University of Miami. “It’s a very interesting experimental observation. But whether this applies to people or not is unknown.”

Extending the findings to another species would be useful, he added. “If you could verify that these same sort of changes could occur in another species, you’d be making the case that this is a paradigm of biology. And you could explore how to manipulate this.”

Sofroniew hopes to be able to apply the work to humans someday. He hopes that drugs or growth hormones could be used to assist nerve growth and spur recovery. Partial spinal cord injuries in particular, or injuries where some tissue is spared, could benefit. It’s possible, he speculated, that similar connections are already being made in humans, “but we’re not getting them to work properly.”

“We want to look at ways in which we can try and get these guys to grow,” he said. “Our study suggests this is something worth trying to do.”