Paralyzed Rats Walk Again
SUNDAY Sept. 20, 2009 -- A three-pronged approach to treating spinal cord injuries allowed paralyzed rats to walk without receiving signals from the brain, scientists report.
Spinal cord injuries result in paralysis when the nerve fibers that carry information to and from the brain are damaged or severed. Much of the focus of research into spinal cord injuries has been exploring ways of regenerating those nerve fibers and connections, which has so far met with limited success in people.
In the new study, rats were treated with a combination of drugs, electrical stimulation of the spinal cord and locomotor training, a rehabilitation technique. The combined treatment enabled the rats to walk with a near-normal gait on a treadmill, without the muscles receiving signals from the brain.
"The study demonstrates that the lower spinal cord has circuitry that is sufficient to support virtually normal, weight-bearing locomotion," said senior study author V. Reggie Edgerton, a professor of physiological sciences and neurobiology at the University of California, Los Angeles.
The study appears in the Sept. 20 online edition of Nature Neuroscience.
Previous research has been able to coax a stepping motion using one or two of those techniques, said Susan Howley, executive vice president of research for the Christopher & Dana Reeve Foundation, which provided some funding for the current research. But this is the first study to achieve actual weight-bearing walking, as opposed to the motions of walking.
"The thing that's very exciting about this is that for the first time they actually showed they can get these rats, with no input from the brain, to step near normally," Howley said. "On the treadmill, they were able to bear weight and step virtually as well as they had been prior to the injury. That's a remarkable achievement."
In the study, researchers put rats whose lower legs were paralyzed in a harness on a slow-moving treadmill and gave them a drug called quipazine, a serotonin agonist that enhances the function of the spinal nerve circuitry. The researchers then used an epidural to apply electrical currents to the dura of the spinal cord, the protective membrane that surrounds it, below the point of injury.
The combination of drugs and electrical stimulation caused the rats to begin walking. Several weeks of daily locomotor training on the treadmill enabled near-normal weight-bearing walking -- including backward, sideways and running.
Because the brain was still unable to direct the walking, the rats could only walk when hooked up to electrical stimulation on the treadmill.
Previous studies have shown that the nerve circuitry of the spinal cord is able to generate rhythmic activity that can direct leg muscles to step, the researchers said. With the right input, the nerves can learn to interpret sensory information from the stepping motion even without help from the brain.
"Previous research has shown the spinal cord can learn whatever task it's being trained to do," Edgerton said. "The spinal cord can interpret the sensory information associated with the stepping, respond to that sensory information and sustain the stepping based on the sensory information."
Locomotive training is a rehabilitation technique that uses that concept to retrain the spinal cord circuitry after injury. Widely used in some European countries, locomotor training involves placing people with spinal cord injuries in harnesses while physical therapists move their legs in a walking motion.
People who undergo locomotor training often see improvements in respiration, bladder function, blood sugar levels and circulation below the level of the lesion, which can help prevent the skin breakdown that can occur as a result of paralysis, Howley said. Others even recover trunk stability, which can enable them to move from a bed to a wheelchair, or a wheelchair to a car, without assistance.
Though a treatment using the three-pronged approach is at least several years away, the study suggests the potential of using neuroprosthetic devices to activate spinal cord rhythmic circuitry, said study author Gregoire Courtine, a professor in the department of neurology at the University of Zurich in Switzerland. His team is currently developing a device that they hope to begin testing in small clinical trials in three to four years.
About 5.6 million Americans, or one in 50, has some level of paralysis, according to a survey released in April of 33,000 U.S. households by the Christopher & Dana Reeve Foundation. About one-quarter of the nearly 2 percent of the U.S. population living with paralysis is due to a spinal cord injury.
The Christopher & Dana Reeve Foundation has more on the latest spinal cord injury research.
Posted: September 2009