By employing a combination of drugs, electrical stimulation, and robot-assisted rehabilitation, researchers have restored a remarkable degree of voluntary movement in rats paralyzed by a spinal cord injury. After several weeks of treatment, the rodents were able to walk—with some assistance—to retrieve a piece of food, even going up stairs or climbing over a small barrier to get it. The rats' recovery raises hopes that a similar combination strategy could help restore movement in some people with spinal injuries. Indeed, such efforts are already underway.
Spinal injuries cause paralysis because they sever or crush nerve fibers that connect the brain to neurons in the spinal cord that move muscles throughout the body. These fibers, or axons, are the long extensions that convey signals from one end of a neuron to another, and unfortunately, they don't regrow in adults. That's why paralysis from a spinal injury is a lifelong disability. Restoring axons' ability to regrow using growth factors, stem cells, or other therapies has been a longstanding—but frustratingly elusive—goal for researchers.
The new study, which appears in Science today, takes a different approach. Instead of trying to repair the main information superhighway from the brain to the body, Grégoire Courtine, of the Swiss Federal Institute of Technology in Lausanne, and colleagues focused on alternative routes. Most spinal injuries in people do not sever the spinal cord completely, explains Courtine. To approximate this situation in rats, his team made two surgical cuts in the spinal cord, severing all of the direct connections from the brain, but leaving some tissue intact in between the cuts. Then they had the rodents begin a rehab regime intended to bypass the fractured freeway, as it were, by pushing more traffic onto neural back roads and building more of them.
This regime, which began about a week after the rats were injured, lasted about 30 minutes a day. During each session, the researchers injected the animals with a cocktail of drugs to improve the function of rats' neural circuits in the part of the spinal cord involved in leg movements, and they stimulated this area with electrodes. With its spinal cord thus primed for action, a rat was fitted into a harness attached to a robotic device that supported its weight and allowed it to walk forward on its hind legs to the extent that it was able. At first, the rats could not move their legs at all, let alone walk.
But after 2 or 3 weeks, the rodents began taking steps toward a piece of food after a gentle nudge from the robot. By 5 or 6 weeks, they were able to initiate movement on their own and walk to get the food. And after a few additional weeks of intensified rehab, they were able to walk up rat-sized stairs and climb over a small barrier placed in their path. Rats that did not undergo rehab, in contrast, showed no improvement at all. Rats suspended over a moving treadmill that elicited reflex-like stepping movement, did not improve either, suggesting that full recovery depends on making intentional movements, not just any movement.
"It's a really remarkable finding," says Michael Beattie, a neuroscientist at the Brain and Spinal Injury Center at the University of California, San Francisco. Additional experiments in the paper make a compelling case that the rats' recovery is due to new neural connections forming to create a detour around the injury, he says. Beattie notes that Courtine's work suggests that all three components of the rehab strategy—the drugs, the electrical stimulation, and the robot-assisted physical therapy—seem to be necessary to maximize recovery. "I think that it actually provides a lot of hope that this kind of strategy will have a big payoff" in people, Beattie concludes.
A case study published last year reported some recovery of voluntary movements in a man paralyzed in a vehicle accident, after he underwent a combination of electrical stimulation and physical therapy. The new rodent research provides a potential explanation for that patient's recovery, says one of the lead authors of the case study, neuroscientist V. Reggie Edgerton at the University of California, Los Angeles. Edgerton says two more patients are undergoing similar rehab now, and his group hopes to add drug therapy to enhance nerve repair in the future. "We're not there yet," he says. "But the bottom line is, things are still looking good."
As encouraging as the new findings are, Courtine is careful to note the strategy's limitations. For one thing, it wouldn't work if the spinal cord were completely severed. In addition, treated rats could only make voluntary movements while the electrical stimulation was turned on, and the same was mostly true of the patient Edgerton and colleagues worked with. "This is not a cure for spinal cord injury," Courtine says. "It's a promising proof of principle."