PHILADELPHIA - Severe injury to the spinal cord can lead to devastating loss of function, and subsequent recovery is often minimal. Accordingly, the factors that inhibit recovery have been a major research focus in recent years. Might there be ways to promote regeneration of the cells in the spinal cord or otherwise encourage a restoration of function following injury?
A new study conducted in mice by researchers at The Wistar Institute suggests that the key to recovery from severe spinal-cord injury may lie in limiting the scarring process that generally follows such an injury, rather than in an enhanced regenerative capacity.
In mice where the ability of inflammatory cells to reach the injury site was physically limited, the formation of scar tissue at the site was also limited, the scientists found in their experiments. Without the physical barrier of scar tissue to impede their progress, neurons on both sides of the injury site were able to grow and reestablish connections with each other over a period of two to three weeks, leading to substantial recovery of function. A report on the study appears in the February 1 issue of the Journal of Neuroscience Research.
"The problem in recovery from spinal-cord injury appears to be the scar tissue that forms in response to injury," says Ellen Heber-Katz, Ph.D., a professor at The Wistar Institute and senior author on the study. "The scar eliminates the ability of neurons to regrow their axons across the injury site. It's an absolute physical block. We found, however, that if you prevent the scar tissue from forming, the mice recover from their injuries."
The findings show that physically preventing scar tissue from forming can open the way for recovery from spinal-cord injury, according the Heber-Katz.
More clinically relevant, perhaps, is that the research also suggests that drugs able to biochemically block scar-tissue formation immediately following such an injury might have a similarly beneficial effect. Perhaps most tantalizing is the possibility raised by the study that therapies designed to eliminate existing scar tissue at the site of past injuries might also be helpful.
"In combination with efforts to address the issue of tissue loss that often accompanies injuries to the human spinal cord, this approach might enable us to design an elegant therapy that permits the cord to heal itself," says Alexander Seitz, M.D., a postdoctoral fellow in the Heber-Katz laboratory and lead author on the study.
To prevent the formation of scar tissue at the site of injury to the spinal cord, the researchers were careful in their experiments to maintain the integrity of the dura, the outer layer of protective membranes that encloses the spinal cord. Doing this left both ends of the damaged cord in close proximity to each other and limited their displacement. It also had the effect of blocking inflammatory cells, particularly the fibroblasts that would normally migrate to the injury site, from being able to reach the site and subsequently proliferate in the gap between the cord ends, leading to scar formation. Scar tissue, a long-lasting protein matrix, is important in the body's response to injury, but it represents an absolute barrier for the axonal growth cones of neurons that might otherwise bridge the injury site.
In addition to senior author Heber-Katz and lead author Seitz, the remaining author on the Journal of Neuroscience Research study is Elsa Aglow, also at The Wistar Institute.
The research has been generously funded from its inception by the G. Harold and Leila Y. Mathers Charitable Foundation, a private foundation based in Mount Kisco, NY. Recently, the work has also received substantial funding from the F.M. Kirby Foundation in Morristown, NJ, and the National Institutes of Health.
The Wistar Institute is an independent nonprofit research institution dedicated to discovering the causes and cures for major diseases, including cancer, AIDS, autoimmune disorders, and other illnesses. The Institute is a National Cancer Institute-designated Cancer Center - one of the nation's first, funded continuously since 1972, and one of only eight focused on basic research. Founded in 1892, Wistar was the first independent institution devoted to medical research and training in the nation. Discoveries at Wistar have led to the development of vaccines for such diseases as rabies, and rubella, the identification of genes associated with breast, lung, and prostate cancer, and the development of monoclonal antibodies and other significant research technologies and tools.
Materials provided by Wistar Institute. Note: Content may be edited for style and length.
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