Earlier work by the researchers had pinpointed genes that were turned on or off after trauma to the brain or spinal cord, and many of these were found to be involved in activating the "cell cycle," which is required for glial cells to grow and divide. This proliferation produces a "glial scar" that can limit recovery. The same process also activates a type of glial cell, called microglia, that are involved in brain inflammation after injury.

At the same time, the cell cycle in neurons is activated, but because these nerve cells can no longer divide, they die. Combined with inflammation, this wave of damage then continues to progressively kill vital brain cells, the researchers have found.

"We reasoned that if you can shut down this delayed response to injury, then the lesion won't spread, the scar won't form, and you could save a lot of tissue that would have died," said Simone Di Giovanni, MD, PhD, an Instructor in Department Neuroscience and first author on the paper.

To stop this damage, the researchers chose to test three drugs (flavopiridol, roscovitine and olomucine) that have been specifically designed to halt activation of the cell cycle. All three worked to stop progressive damage when tested in laboratory cell cultures. They then examined the use of flavopiridol in an experimental rat model of traumatic brain injury.

Flavopiridol, an anticancer drug, has already been tested in humans, but has not been proven successful because of the toxicity associated with sustained use, said Di Giovanni. But the researchers thought that it might work, and with limited side effects, if the drug was used just once.

So, in this study, they delivered flavopiridol to the animals 30 minutes after brain injury and found that it reduced expression of proteins that activated the cell
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Contact: Laura Cavender
lsc6@georgetown.edu
202-687-5100
Georgetown University Medical Center
16-May-2005