Friday, November 10, 2006
Finding surprises researchers, who discovered that young rats mend more quickly because cells near the injury site respond differently than in adults
Neuroscientists had long believed that the only way to repair a spinal cord injury was to grow new neural connections, but researchers at Georgetown University Medical Center have found that, especially in young rats, powerful cells near the injury site also work overtime to restrict nerve damage and restore movement and sensation.
The same process does not work as efficiently in adult rats and thus recovery time is much longer, the researchers also discovered. But they say that now that they know such a mechanism exists, it may be possible one day to “switch” these cells on therapeutically ? and possibly help humans function better following serious spinal cord injuries.
“No one knew cells in the spinal cord acted to protect nerves in this way, so it gives us some hope that in the future we could stimulate this process in the clinic to enhance recovery and ensure the best outcome possible for patients,” said the senior author, Jean R. Wrathall, Ph.D., professor in the Department of Neuroscience.
“This is an animal study, however, and there is much work to do to understand more about this process and how it might be altered,” Wrathall said. The study, whose first author is graduate student Philberta Y. Leung, is published in the November 2006 issue of the journal Experimental Neurology.
At the least, Wrathall said, the study reveals surprising new information about nerve cell recovery that neuroscientists can now explore.
In vertebrates, the nervous system uses a two-way transmission system to communicate the electrical impulses that lead to muscle movement and the perception of sensation. In humans, hundreds of thousands of nerve fibers (axons), which can be several feet in length, run through the spinal cord like a two-lane road. Half of these axons connect the brain to distant muscles, and the other half links the body to the brain.
Axons cannot regenerate when they are completely severed, but researchers believe that in a partial injury, surviving nearby axons that serve the same general body area and function can “sprout” new connections to those injured nerve cells that have lost some of their axons. In studying spinal cord injury in rats ? the usual model for this kind of investigation ? researchers had thought that younger rats (“pups”) regain function faster because this sprouting occurs more quickly and proficiently than in older rats. “Just as young trees grow more quickly if you prune them than do older trees, we thought than in young animals, surviving axons would sprout new, and longer, axonal connections more readily,” Wrathall said.
But the findings surprised them. “We didn’t see that sprouting was faster or better in younger than in adult rats after a partial spinal cord injury,” she said. Instead, they saw distinctions in what occurred in cells within the spinal cord at the site of injury. Leung and Wrathall specifically discovered that in the pups, specialized neural stem cells grew vigorously after injury and within one week, many oligodendrocytes, cells whose function is to provide a protective myelin sheath to axons, were produced..
The researchers believe that these activated cells wrap nearby surviving axons with extra myelin sheathing in order to protect them and support their function after injury.
“The ability of axons to transmit their signals is greatly dependent on the insulation provided by their myelin sheaths, and we know that axons near the site of injury eventually can die due to loss of this myelin,” Wrathall said. “So we believe these stem cells work to protect healthy axons against toxic factors in the microevironment.”
Adult rats do not activate these specialized cells to the same extent as the pups do after injury, for reasons that are not understood, she added.
“We hadn’t expected these results, but they are exciting for the field of spinal cord injury and recovery,” Wrathall said. “Now that we know that the difference in the local cell response to injury means a quicker recovery, we might be able to eventually exploit that innate healing ability in humans.”
She added that these new findings might also be relevant to multiple sclerosis, a disease caused by loss of an axon’s protective myelin sheath.
The study was funded by grants from the National Institutes of Health
About Georgetown University Medical Center
Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through our partnership with MedStar Health). Our mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, the world-renowned Lombardi Comprehensive Cancer Center and the Biomedical Graduate Research Organization (BGRO).