Rats paralyzed by spinal-cord injury can learn to control their hind limbs again if they are trained to walk in a rehabilitative device while their lower spine is electrically and chemically stimulated. A clinical trial using a similar system built for humans could begin in the next few years.
Researchers in Switzerland used electrical and chemical stimulation to excite neurons in the lower spinal cord of paralyzed rats while the rodents were suspended by a vest that forced them to walk using only their hind legs. The rehabilitative procedure led to the creation of new neuronal connections between the movement-directing motor cortex of the brain and the lower spine.
Plans are under way to develop a human-sized version of the training system and to test its effects in clinical trials in Europe. Researchers at the Swiss Federal Institute of Technology and other European institutions are also working on an improved, implantable version of the electrical spinal stimulation system that may find its way into humans next year.
After training in a supportive robotic device while receiving spinal stimulation, a rat paralyzed by a spinal-cord injury regained enough control of its hind limbs to climb stairs.
EPFL (Swiss Federal Institute of Technology)
Courtine had previously shown that this type of automatic walking could initiate walking patterns in the hind limbs of spinal-cord-injured rats that were spinally stimulated while on a treadmill. Because the spinal column could control the walking pattern, Courtine suspected that only a weak signal from the brain would be necessary for the animals to start walking voluntarily.
To test whether the rats could recover brain-directed control of these movements, he and his team developed a robotic support system that suspends rats in a bipedal standing posture and helps with balance but does not provide any forward momentum. Ten paralyzed rats were trained daily to walk with stimulation both on a treadmill and in the robotic system. After two to three weeks, the rats took their first voluntary steps. “This is the first time we have seen voluntary control of locomotion in an animal with [an injury] that normally leaves it completely paralyzed,” says Courtine.
Key to this recovery was the active role of the rat’s brain in wanting to move forward. The electrical and chemical stimulation puts the rat’s nervous system in a state where walking is possible, says study co-author Janine Heutschi, and “then you need to make the rat to want to walk.” The rats’ desire to walk was motivated by chocolate rewards and vocal encouragement from the researchers. The robotic suspension system forces the rodents to use their dormant hind limbs and not drag themselves forward with their still functional forelimbs.
The combination of electrochemical stimulation and active training, which included walking up stairs and around obstacles, resulted in new neuronal connections that bypassed the site of injury. “We promoted extensive remodeling of the neuronal connections not only at the site of the injury but throughout the central nervous system, including in the brain,” says Courtine. What was most surprising, he says, was the fourfold increase in neuronal projections sent to the brain stem from the motor cortex, which provides conscious control of movements. “The motor cortex becomes the maestro of the reorganization process.
The conscious intent of the rats was necessary for the remodeling as well. The nervous systems of rats that received the electrochemical stimulation but trained only on treadmills did not demonstrate the anatomical changes. “You need to incorporate an input from the brain,” says Heutschi. “It doesn’t work if the rat is on a treadmill; you have to force them to use the brain to control their hind limbs.”
Experts think the results are promising for those spinal-cord-injured patients who do not have a complete cut through the cord. Even though all connections between the brain and the lower spinal cord were disrupted in the experimental rats, “there are some remaining fibers, so the beauty of their technology is using the robotic training system to activate those remaining connections that can allow the cortex to control the limbs and to regain voluntary movement,” says Zhigang He.