LEXINGTON, KY (July 26, 1999) - Spinal cord injuries result from damage to cells during the weeks following the injury as well as at the time of the trauma. In the August issue of Nature Medicine, University of Kentucky College of Medicine researchers report the discovery of the molecular signals that lead to apoptosis, or programmed cell death, following spinal cord injury.
"This work represents a major advancement in our understanding of how and why cells in the spinal cord die following injury," said Joe Springer, Ph.D., associate professor, Department of Anatomy and Neurobiology, UK College of Medicine, and lead author of the paper. "This study will be important in directing future research efforts, including the development of drugs to limit the consequences of spinal cord injury."
About 250,000 Americans have spinal cord injuries, and about 10,000 new cases occur each year. In Kentucky, about 1,100 people suffer from spinal cord injuries with about 200 new cases each year.
People between the ages of 16 and 30 account for more than half of all spinal cord injuries, and spinal cord injuries are three times more prevalent in males than females.
The incidence of spinal cord injuries is rare compared to other health problems, such as heart disease, cancer or stroke. However, the total financial burden of spinal cord injuries is disproportionately high. The estimated cost of spinal cord injuries in the United States was $7.7 billion in 1995, and a 27-year-old with complete quadriplegia will incur lifetime costs of about $1 million.
Apoptosis is a "suicide" process. The dying cell activates internal biochemical reactions, such as fragmentation of the DNA, to disassemble itself systematically. One cell type that undergoes apoptosis after the injury is the oligodendroglia, which provides myelin to the nerves controlling motor function. Myelin acts as an essential insulator of nerves, and without myelin, the nerves do not function properly, contributing to paralysis.
"Through molecular signals, the injury spreads throughout the spinal cord," said Pamela Knapp, Ph.D., assistant professor, Department of Anatomy and Neurobiology, UK College of Medicine, and co-author of the paper. "The oligodendroglia, although undamaged by the original injury, can die in the weeks following the trauma. By developing therapeutic strategies that can prevent the death of the oligodendroglia by inhibiting the apoptotic molecular pathway, we hope to promote nerve function and improve recovery from spinal cord injury."
The caspase family of proteases, enzymes that destroy proteins by breaking them into individual amino acids, regulates apoptosis in humans and other mammals. This research clearly shows that in cells that are damaged by spinal cord injuries, the release of a protein called cytochrome c from the mitochondria causes the proteins Apaf-1 and procaspase-9 to bind together. This, in turn, activates caspase-3 which then cleaves several proteins (gelsolin, PAK2, fodrin, and DFF40/CAD), resulting in DNA fragmentation and destruction of the cellular structure. These molecular signals then spread to surrounding areas of the spinal cord.
This research project was one of the first supported by the Kentucky Spinal Cord and Head Injury Research Trust (KSCHIRT). Established by the 1994 General Assembly of the Commonwealth of Kentucky, KSCHIRT allocates funds to support spinal cord and head injury research at UK and the University of Louisville with the major goals of understanding how cells die following head or spinal cord injury and identifying effective therapeutic treatments.
"The UK Chandler Medical Center has several established clinical and basic scientists investigating spinal cord and head injury," Springer said. "With continued support from KSCHIRT and other funding organizations, the UK Chandler Medical Center clearly has the potential to become an internationally-recognized leader in discovering effective ways to treat people suffering from these devastating injuries."
Robert Azbill, a graduate student in the Department of Anatomy and Neurobiology, UK College of Medicine, also contributed to the paper.
The above story is based on materials provided by University Of Kentucky Medical Center. Note: Materials may be edited for content and length.
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