AFTER CUTTING THE CORD: Scientists showed that intrinsic spine neurons can substitute for long nerve fibers (which connect directly to the brain) that are severed in spinal cord injury to restore walking ability. Image: © ISTOCKPHOTO/SEBASTIAN KAULITZKI
Often spinal cord injuries result in the severing of the long nerve fibers connecting the brain to the spinal cord, disrupting one's ability to walk, among other things. But even with the primary top-to-bottom signal highway rendered out of order, the nervous system can, over time, reroute itself, finding neural detours and side streets that restore movement, according to a new study out of the University of California, Los Angeles (U.C.L.A.).
"It's been known for some time that after certain types of lesions, animals and human[s] will recover their ability to walk," notes Michael Sofroniew, a professor of neurobiology at U.C.L.A.'s David Geffen School of Medicine. For instance, if the long nerve fibers on only one side of the spinal cord are damaged, "the previous explanation is that the other [intact] side was able to activate things," he adds.
Recent work in Sofroniew's lab contradicts that theory. Using mice, the U.C.L.A. researchers first severed the nerve fibers coming from the brain to one side of lumbar spinal cord (in the lower back), which controls walking. This resulted in a complete loss of movement in the corresponding hind limb, causing the animal to drag it along when it moved. Over a period of 10 weeks, Sofroniew says, "the swing of the injured leg starts coming back and gets to become 80 percent of normal," on average.
If the relay neurons in the spinal cord located near the area where the injury occurred were chemically blocked, however, the restoration of movement disappeared. "That basically proves that these cells are essential for the recovered function," Sofroniew explains. But it leaves open the possibility that the still-intact long nerve fibers on the other side of the spinal cord may be contributing to this recovery.
So the team repeated the study, again severing the nerves on one side of the lumbar spine and letting function return via new connections. Then they damaged the nerves on the other side of the lower spinal cord as well. Between the two injuries was a zone of spinal cord tissue left unharmed.
Without help from long nerve fibers from the brain on either side spinal cord, which, at this point, were both cut from their normal connections, the mouse could still recover walking function, implying that the intact zone of relay neurons in the spinal cord had been able to transmit signals from the brain and restore movement.
"It should be emphasized that the final walking that the mice had at the end was not as fast, not nearly as efficient," Sofroniew notes. Again, when the unharmed zone was chemically disrupted, the mouse's ability to walk disappeared.
The U.C.L.A. team next hopes to determine how to enhance signal rerouting from the brain to the spinal walking centers. Sofroniew believes that prodding these intrinsic spinal cord neurons with drugs to form new connections combined with physical rehabilitation programs may maximize patient recovery.
Karim Fouad, an associate professor of rehabilitation medicine at the University of Alberta in Edmonton, says that the new work firmly establishes that these "interneurons" that make up the spinal cord can substitute to receive the signals that control movement when long nerve fibers are damaged. He adds, however, that the proposed path to maximizing recovery from spinal cord damage has already been explored in two papers he co-authored in the journal Brain.
"We actually showed just recently that if we give a certain drug to the brain, we can promote this rewiring into these 'interneurons'," he explains, referring to a 2006 study in rats involving brain-derived neurotrophic factor (BDNF), a protein that encouraged new connections between neurons in the brain and the relay neurons in the spinal cord. Further, in a study published last year, his lab demonstrated that reaching exercises undertaken by animals also encouraged the creation of these connections.