These injuries occur when a sudden physical assault on the head causes damage that disrupts normal brain function. The major causes of head trauma are motor vehicle accidents, falls and violence.

Supported by a National Institute of Neurological Diseases and Stroke grant, researchers at the Evelyn F. and William L. McKnight Brain Institute of UF, in conjunction with those at the Medical College of Virginia, will work to help patients recover by limiting some of the secondary damage, such as swelling, that occurs after brain injury. UF's portion of the grant is $605,000.

Researchers will use a common chemotherapy drug to treat these delayed reactions that lead to brain cell death. The treatment will be administered to people with new severe traumatic brain injuries, and it will be the first time the drug is used to treat these injuries. UF's clinical trials will be conducted at Shands at UF medical center.

If the therapy successfully halts brain cell death in injuries caused by trauma, UF researchers hope it may be effective for treating other conditions involving similar reactions that harm the central nervous system, such as stroke, hemorrhage and tumors.

"Management of patients has improved over the last 20 years, and the mortality rate has dropped in half, but there is no treatment so there are more people surviving with significant disabilities," said Ronald Hayes, Ph.D., a co-investigator on the grant. Hayes directs the Center for Traumatic Brain Injury Studies at UF's McKnight Brain Institute.

More than 5 million people in the United States live with disabilities associated with traumatic brain injury, according to the Centers for Disease Control and Prevention.

UF researchers theorize that head injury damages the nerve cells in the brain rendering them less able to regulate the flow of chemicals, particularly calcium, into and out of the cell. When calcium builds up inside the cell, it causes progressive damage to the mitochondria, the energy-producing machinery of the cell, and ultimately kills nerve cells.

"We're trying to separate the events associated with head injury that are primary -- meaning they're a product of the injury itself -- from the reactions or misdirected healing attempts by the body that end up being more destructive than the actual injury," said A. Joseph Layon, M.D., a professor of critical care medicine in the department of anesthesiology, who is directing the study.

"For instance, when a prize fighter is knocked out, the brain swelling occurring at the site of the traumatized brain is a delayed reaction that by itself might do secondary damage, without which the recovery might have been better," Layon said.

UF researchers hope to prevent the delayed responses that result in cell death by treating severe brain injury victims quickly -- within the first 12 hours of the injury -- with a commonly used cancer chemotherapy agent called Cyclosporin A.

In animal studies, the drug has been shown to regulate the influx of calcium into the cells, blocking the mechanisms that injure mitochondria. Toxicity is unlikely because Cyclosporin A has a long history of administration for other indications, the researchers say.

In randomized fashion, a low dose of the drug, or a placebo, will be administered through an intravenous catheter to patients who sustain severe head injury and arrive at the hospital within eight hours of the injury.

Brain levels of the drug will be evaluated through a catheter inserted parallel to a tube routinely placed to measure and regulate the pressure inside the brain. The catheter also will be used to sample substances liberated by the brain over a 72-hour period in order to determine the treatment's effectiveness.

"We will look at these substances to determine whether they contain breakdown products indicative of nerve cell death, and also to understand the cascade of events that happen in the brain after severe traumatic brain injury," Layon said.

"The alterations done to the brain by trauma induce many of the same cellular reactions common to injuries that damage the central nervous system, such as stroke. This technology really gives us a chance to look at brain metabolism and metabolic byproducts, and determine the value of this treatment for a host of other acute central nervous system conditions," he added. - By Arline Phillips-Han

08-May-2002