Charles Greer is taking what might be considered an unconventional approach to his medical research: He's looking at cells in the nose to help repair damaged cells in the spine. Greer's laboratory studies involving olfactory nerve cells have put him in the forefront of spinal cord research -- and garnered a $4.5 million grant from the National Institutes of Health (NIH). The Yale scientist and his colleagues have been seeking a viable way to restimulate the impaired area of a damaged spinal cord. "We were looking for a population of cells we thought would support nerve cell regrowth," says Greer, who is professor of neurosurgery and neurobiology, director of the Spinal Cord Research Program and vice chair for academic and research affairs in neurosurgery. The researchers believe it is possible to stimulate groups of nerve cells -- or axons -- in the spinal cord that are inactive by interjecting cells from other areas of the body that have displayed a capacity to regenerate themselves and adapt to changes in the cellular environment. This characteristic, called plasticity, is found in axons in the nose. The scientists hope that, when transplanted, the olfactory cells will act as a "bridge" that will help link severed spinal cord nerves. Greer's co-investigators are Jeffery Kocsis, professor of neurology and neurobiology, and Anthony van den Pol, professor of neurosurgery. "Our primary objective is to identify a mechanism that will be manipulated to create axonal extension," Greer notes. "We needed to find a population of cells that would support axonal growth effectively and reliably through the site of the lesion. There was lots of interest in the olfactory system because of its capacity for this kind of plasticity." Scientists, Greer explains, have observed that cells in the nose repeatedly regenerate themselves. If the mechanisms associated with that propensity for regrowth could be isolated and understood, they could be applied to other areas of the body -- such as the spinal cord -- he says. The NIH has long supported spinal cord research at Yale, beginning with the work of Professor Emeritus Dr. William F. Collins, a former chief of surgery, who secured the first NIH grant for spinal cord research 25 years ago. This latest grant will extend that funding for four years, allowing the Yale scientists to continue to build on Collins' work, according to Greer. "What drove the initial submission of the grant was the recognition of the persistent pain and suffering experienced by patients with spinal cord injuries," says Greer. Along with physical pain, he notes, psychological distress also is associated with spinal cord injuries. "Christopher Reeve, for example, talks about the possibility of just being able to move a finger," says Greer. "If he could move one finger, he could control a computer. He could 'rule the world.'" The spinal cord is a shaft of nervous tissue, about one-quarter inch in diameter, extending from the brain down the back. Impulses are carried to and from the brain through the cord. Although scientists have been documenting studies of the spinal cord since the mid-19th century, actor Reeve's 1995 horseback riding accident helped propel the devastating effect of spinal cord injuries into public consciousness. Any damage to the spinal cord is considered potentially serious, notes Greer, with the location and extent of the initial injury dictating the severity of the resulting impairment. A common result is paralysis, due to the severing of nerves usually associated with a spinal cord injury. In Reeve's case, two fractured vertebrae along the spinal column -- which protects the spinal cord -- damaged the cord and rendered the actor paralyzed from the neck down. When the spinal cord is damaged, Greer explains, the formation of scar tissue -- called reactive gliosis -- occurs at the site of the injury. The result is a glial scar which can deter recovery by forming a barrier prohibiting the regrowth of nerve cells. The scientists originally looked at ways the central nervous system might be able to adapt to injury and repair itself, says Greer. Now, 20 years later, they have decided to narrow their focus. Greer, Kocsis and van den Pol are concentrating specifically on the olfactory system's ensheathing cells, a group of cells that favorably support growth. Ensheathing cells are present during olfactory-nerve formation and are thought to aid the system's axonal expansion and path-finding mechanisms. "We found that axonal growth is better with ensheathing cells," says Greer. "Our results have been consistent with other studies." Through in vitro and in vivo studies, the scientists transplant ensheathing cells into cellular environments ordinarily resistant to axonal development (such as the site of a glial scar). What they are finding is that the ensheathing cells actually act as a "guide" for axons, accompanying and directing them across the inhospitable area. The hope is that when transplanted into an injured human spinal cord, these ensheathing cells will increase the likelihood of axonal survival and functionality -- which opens the possibility of reversing a neurological deficit caused by spinal cord injury. However, warns Greer, much more work is needed before human trials of this technique can begin. "Spinal cord injuries carry a huge cost to society," Greer says. "Through the pursuit of the studies, we hope to reduce that cost by learning more about the capacity of the nervous system for plasticity -- and in doing so, setting the stage for transplants as a viable option." -- By Felicia Hunter T H I SW E E K ' SS T O R I E S Yale students working with city residents to revitalize New Haven . . . 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Charles Greer