Treatment helps paralyzed rats walk

Combination of drugs, electrical stimulation and therapy restores lost connections

Web edition : 2:07 pm

Scientists have trained paralyzed rats to walk, run and even climb stairs. Weeks of rigorous practice coupled with an electrochemical spine-stimulating regimen allowed the animals to overcome devastating spinal cord injuries that immobilized their rear legs, Swiss scientists report in the June 1 Science.

Although preliminary, the results offer hope to people paralyzed by spinal cord injuries. ?The really exciting thing, the take-home message for people living with spinal cord injuries, is that this represents yet another step towards real treatment,? says neurologist John McDonald of the Kennedy Krieger Institute in Baltimore and the Johns Hopkins University School of Medicine. ?The real beauty is that this is not something that would necessarily have to go through 10 years of FDA approval.?

Recovery, the Swiss team found, relied on a combination of treatments, all readily adaptable to humans: Nerve cells in the spine below the damaged site were stimulated with a cocktail of drugs similar to some antidepressants. Electrical shocks, delivered via electrodes, also activated the spine. In this way, the researchers primed the rats for the next stage of treatment ? learning to walk again.

A stabilizing robotic harness held each treated rat upright on its hind legs and kept it from tipping over sideways, a device that study coauthor Gr?goire Courtine of the Swiss Federal Institute of Technology in Lausanne likens to two very strong physical therapists. The animals were then tempted with cheese and chocolate ? a situation that drove the rats to try very hard to move forward.

?The brain is maximally engaged and willing to do anything to reach its reward,? says Courtine. After several weeks of training, the formerly paralyzed rats began taking voluntary steps toward their treats. Astonished, Courtine says he and his colleagues kept pushing the rats to do more and more sophisticated voluntary movements. More training allowed the animals to run, climb stairs and even avoid obstacles in their paths. The stronger animals were even able to bear their entire body weight on their two back legs.

It turns out that motivation is crucial, and not just because the obstacles are so great. Prompted by a moving treadmill, rats that received the electrochemical treatment could put one foot in front of the other, but this kind of movement was automatic and didn?t involve the brain. Rats could walk voluntarily only when the training included the motivating treat.

Experiments on the animals? brains and spinal cords revealed that the nervous system had rewired itself in many different ways by sprouting detours around the injury site. Actively trained rats had new nerve fibers running from the brain down to the spinal cord. These rats also had changes far away from the injury site in the motor cortex, the part of the brain that controls leg movements. The brains of rats trained only on treadmills showed no changes in their brains.

The finding fits in with a growing realization that this sort of active rehabilitation ? in which a person is maximally engaged and that uses electrodes to stimulate paralyzed muscles ? works, McDonald says. McDonald used similar techniques to help actor Christopher Reeve regain some voluntary control over select muscles years after his spinal cord injury left him paralyzed.

Most spinal cord injuries in people result from severe bruising, which can leave some remaining tissue to bridge the spinal cord to the brain. The Swiss team studied rats with two staggered, incomplete snips to their spinal cords, which completely paralyzed the animals? hind legs but also left an island of intact spinal cord tissue between the damage sites and the brain.

The study raises some questions, such as whether the technique will work for the more common kind of bruise-induced injury, and whether other movements will also show an improvement. Fine hand or finger control, for instance, might require a different kind of training regimen, says neuroscientist Michael Beattie of the University of California, San Francisco. Balance may also require a different kind of training. Some of the more successful rats were able to walk a few steps on four legs, but quickly lost balance and fell over without the supportive harness.

The Swiss team?s success supports a more principled approach to treating spinal cord injuries, Beattie says. ?Most rehabilitation is done by, ?This should work.? There?s not a lot of evidence-based practice,? he says. The new study, he says, and others like it help scientists understand how rehabilitation can be optimized. ?It may be that people with severe injuries, if they get the right kind of treatment, can perform much better than we thought.?

Courtine and his colleagues are continuing to test their method. Preliminary results suggest that spine-stimulating drugs can be progressively tapered with no loss of benefits. And as part of a project called NeuWalk, Courtine and his colleagues are developing an electrical stimulator for humans. The team hopes to get safety approval for that device in the next two years.

Found in: Body & Brain and Genes & Cells

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