St. Louis, April 27, 1998 -- Several biotech companies are exploring the idea that compounds called caspase inhibitors might minimize the brain damage that results from blood and oxygen shortage. Now researchers at Washington University School of Medicine in St. Louis have shown that one such compound protects newborn rats from damage.
"To our knowledge, this is the first demonstration that delayed treatment with a caspase inhibitor, even when given systemically, can be neuroprotective in an injury model," says David M. Holtzman, M.D., chief author and assistant professor of neurology and molecular biology & pharmacology. "If these compounds prove not to be toxic and are able to come into clinical use, it appears there may be a window of at least several hours when one could administer them."
The findings are published in the May 1 issue of Journal of Clinical Investigation. Former postdoctoral fellow Yu Cheng, M.D., Ph.D., is first author.
An interruption in the supply of blood and oxygen to the brain in the womb or during or after birth is the largest contributor to brain degeneration in children. Life-time consequences include mental retardation, seizures and cerebral palsy, which affects 500,000 Americans.
Holtzman mimics the condition by interrupting the blood supply to one side of a newborn rat's brain and briefly lowering the oxygen content of the air. This procedure kills neurons, which results in loss of brain tissue. Holtzman and colleagues showed, however, that while some neurons swell up and burst, as happens rapidly in adults with head injury or stroke, many neurons slowly shrink through a process resembling cell suicide.
A series of genetically programmed steps lead to cell suicide or apoptosis. The rat brain cells appeared to die this way because their demise was delayed, beginning six hours after the procedure and peaking between 18 and 24 hours. Just before they died, the cells activated their casp
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Contact: Linda Sage
sage@medicine.WUSTL.edu
314-286-0119
Washington University School of Medicine
1-May-1998