In animal studies, researchers from Georgetown University Medical Center have shown how traumatic brain injury leads to loss of brain function - and found that an experimental drug can stop the damage and promote recovery.
In research published in the Proceedings of the National Academy of Sciences (PNAS), the researchers say their findings may hold promise for the treatment of human traumatic brain injury, a condition they say affects almost half a million Americans a year and which is currently untreatable.
“Our research suggests that it might be possible to effectively prevent much of the injury-induced brain damage,” said the study’s principal investigator, Alan Faden, MD, Professor of Neuroscience, Neurology and Pharmacology at Georgetown University Medical Center, and Director of the Laboratory for the Study of Central Nervous System Injury.
“We always have to be cautious in predicting human outcome from a study in rats, but the prevention of brain damage that we saw in this study is nothing short of remarkable,” he said. Rats untreated after head injury were left 28 days later with a large hole in their brain from death of cells surrounded by a scar, whereas the brains in those rats treated with the experimental drug, Flavopiridol, were nearly intact, with cognitive and motor function recovered, Faden said. “These rats were no different from the ones that had not experienced brain injury,” he said.
The approach that Faden and his research team have taken was suggested by findings from extensive gene studies conducted at Georgetown. Rather than trying to stop the earliest damage that results from the direct mechanical injury - the approach that is now most often used clinically - the Georgetown researchers took the tactic of trying to limit a second, and much larger, “wave of damage” which they have found usually peaks from 24-72 hours after injury. During this time, “glial” cells, which provide support and nutrition to neurons (the nerve cells that pass information throughout the brain) are pushed to divide extensively, producing scar tissue, Faden said.
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.