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Experimental Drug Reverses Brain Injury in Rats

Finding could lead to new treatments for traumatic brain injury and stroke

TUESDAY, May 17, 2005 (HealthDayNews) -- An experimental cancer drug has halted and then reversed damage caused by traumatic brain injury in rats, Georgetown University researchers report.

"We used a drug that has never been used before in brain trauma," said lead author Dr. Simone Di Giovanni, an instructor in the university's department of neuroscience. "With that drug, we were able to reverse the brain pathology and brain damage that occurred after brain injury in a traumatic model of brain injury in rats."

In their experiments, Di Giovanni's team injured the brains of rats, some of which were left untreated for 28 days. These animals had a large hole in their brain caused by the death of brain cells. The hole was surrounded by scar tissue.

However, in rats treated with the cancer drug flavopiridol, brains remained nearly normal, the researchers report. In addition, both cognitive and motor function was restored in these animals, Di Giovanni said, with these rodents appearing no different from rats whose brains had not been injured.

Flavopiridol has been tested on human cancer patients but has not been approved due to side effects seen during long-term use, Di Giovanni said.

"In our case, because the delivery is acute, we believe it can be used in a clinical setting, because it is safe in the short-term," he added.

A report on the research was published in the May 16 early online edition of the Proceedings of the National Academy of Sciences.

According to Di Giovanni, flavopiridol works by inhibiting the formation of inflammatory cells that kill other cells and are responsible for causing most of the damage after traumatic injury.

"Inhibiting the proliferation of these cells inhibits the proliferation of other cells in the brain responsible for scar formation," he said. The drug also prevents the death of neurons, Di Giovanni added. "In a way, it's two-birds-with-one-stone."

Di Giovanni believes that flavopiridol would work the same in humans. "Sometimes using drugs that are already available for patients and transferring them to other medical uses can be very effective to test," he said.

An expert who has successfully used flavopiridol to prevent the death of neurons after stroke and Parkinson's in rats finds the new research consistent with his and other findings.

"However, whether this particular drug can be used in humans remains to be seen," cautioned David Park, an associate professor of neuroscience at the University of Ottawa.

Among Park's concerns are how the drug would get into the brain, which has not been tested. "It is difficult to translate animal experiments into humans," he said. "Drugs are notorious for having other effects."

Park believes that blocking cell function is the way to protect the brain after injury or stroke. However, whether flavopiridol is the right drug to use is not clear, he said.

In his stroke experiments, he noted, flavopiridol worked initially but the beneficial effect was not sustained over the long term.

"The hardest thing is, 'How do you design an effective drug that is delivered, is safe, has few side effects, in humans?" Park added. "That's the real bottleneck."

However, he said this line of research is promising and one day will lead to a breakthrough that will make it possible to protect the brain after injury and restore function.

"We're trying," Park added. "But we have to temper our enthusiasm with a high dose of reality, making sure we understand the pitfalls in animal studies."

More information

The National Institute of Neurological Disorders and Stroke can tell you more about traumatic brain injury.

SOURCES: Simone Di Giovanni, M.D., Ph.D., instructor, department of neuroscience, Georgetown University, Washington, D.C.; David Park, Ph.D., associate professor of neuroscience, University of Ottawa, Canada; May 16, 2005, online early edition, Proceedings of the National Academy of Sciences
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