Paralyzed rats run again: Could method help humans?
Paralyzed rats learned to walk, run and spring deftly over obstacles after they were put on a physical training regimen that included electrical and chemical stimulation of their broken spinal columns and a “robotic postural interface,” a new study reveals.
The study, published Thursday in Science, suggests that for humans with spinal cord injury, the trick to regaining lost movement may lie not in regeneration of the severed spinal cord, but in inducing the brain and spinal cord to forge wholly new paths toward each other. The Swiss authors liken that process to the way that infants, their nervous systems incomplete and learning by experience, sync up their brains and limbs so they can progressively crawl, stand, walk and play.
All told, 250,000 Americans live with spinal cord injury, and just over half -- 52% -- are paraplegic. Each year, 11,000 new injuries occur--overwhelming in young males.
In this study, coaxing that neural reinvention along took four key components: a soup of neurotransmitters — serotonin, dopamine and norepinephrine -- injected into the epidural space; a set of electrodes supplying a continuous flow of electrical energy near the site of the break in the spinal cord; a rehabilitation rig that supports the unsteady participant and initially forces movement of the legs; and a training course that is as real-world as possible.
After five to six weeks of training on uneven and irregular terrain, all 10 rats used in the study regained the capacity to walk voluntarily “and even to sprint up a staircase,” says study co-author Gregoire Courtine, a research scientist in spinal cord repair at the Ecole Polytechnique Federale de Lausanne in Switzerland.
“It was pretty exciting,” he said in an interview Thursday.
The experiment brought together many disparate threads of rehabilitation research and was several years in the making. Its 10 rats were paralyzed in a way that mimics many spinal cord injuries that result in paralysis of the lower limbs: The spinal cord is partially severed at two separate but neighboring sites, leaving intact tissue but interrupting the passage of messages from the brain to the legs.
About a week later, training began for 30 minutes a day. First, the neurotransmitter cocktail was introduced into the area of injury, reawakening neurons long dormant. Five to 10 minutes later, researchers sent a steady current of electricity through the chemically-excited neurons that control leg movement.
At first, the rats responded with involuntary movement of the legs. But prodded across challenging obstacles by a supportive robotic prosthetic, the rats’ movements became increasingly intentional.
Two to three weeks into the training, “the first, effortful voluntary steps emerged.”
The regimen brought about changes at the site of the injury that were equally striking: In the rats trained “overground,” as opposed to those that got training only on a treadmill, surviving neurons below the site of the injury began to sprout long tentacles — axons reaching out in the darkness — across the space where the spinal cord had been severed. From the brain’s motor cortex, down through the brainstem and the descending neural pathways, axonal projections reached southward in search of new connections.
Prodded by their hard practice and by rewards like Swiss chocolate, the injured rats grew “de novo brainstem and intraspinal relays” that would find each other across the neural wasteland caused by injury. With five to six weeks of hard work, chemical support and electrical stimulation to the area, the rats built a “detour circuit” around the impassable roadblock of spinal cord rupture. “Voluntary control over sophisticated locomotor movements” was completely restored, the study authors wrote.
Can it work in humans?
“This is not an intervention that will cure spinal cord injury; we need to be realistic here,” Courtine said in an interview. For people with complete or near-complete severing of the spinal cord, the study authors wrote, “undoubtedly, neuroregeneration will be essential.” That may be a job for stem-cell therapies years away from reality.
But this “more immediate approach,” they added, “might capitalize on the remarkable capacity of spared neuronal systems to reorganize” themselves in response to rehabilitation.
Courtine, who conducted much of his preliminary research in the lab of UCLA neurophysiologist Victor Edgerton, said he hopes to initiate Phase 2 trials with human subjects within a couple of years. “What is exciting here is that it’s a different approach, and the results are unprecedented,” Courtine said.