Neuroscientists have found a drug for traumatic brain injury that appears to work better than any current treatment. Rats that were given the drug following a concussive brain injury had a near-complete recovery, while untreated rats suffered significant brain damage.
In the days after a concussion, damaged brain tissue responds in two main ways. Neurons self-destruct in a process called apoptosis, and glial cells, some of which support and surround neurons, divide, causing inflammation and scar tissue. These processes leave a hole surrounded by a glial scar, resulting in loss of motor and cognitive function.
To find a way to prevent this damage from occurring, neuroscientist Simone Di Giovanni and others in Alan Faden's lab at Georgetown University in Washington, D.C., and at the Universita di Pavia in Italy used gene expression arrays to determine which genes become activated in damaged brain tissue after a concussion. They found that cell cycle genes involved in cell division set off both glial proliferation and neuronal apoptosis. The researchers then injected an experimental drug called flavopiridol, which inhibits cell cycle enzymes, into the cerebral fluid of rats 30 minutes after they were given a moderately severe concussion.
Rats that were not treated developed a large hole in their brains visible with magnetic resonance imaging (MRI). But in the treated rats, there was scarcely a trace of brain damage on MRI after 4 weeks, and they performed as well as normal rats on motor and cognitive tests, while brain damaged rats did not. "This degree of protection was really remarkable. Lots of drugs have shown neural protection in similar models, but they haven't provided anywhere near this level of benefit," says Faden, whose group's report appears online this week in the Proceedings of the National Academy of Sciences.
The flavopiridol treatment is a "unique and promising approach," but it's still a long way from the emergency room, cautions neurobiologist Edward Hall of the University of Kentucky in Lexington. First Faden's team needs to see how well the drug works a couple hours after injury, which is how long it might take for an injured person to reach a hospital. So far, they've treated rats at 24 hours and gotten less complete recovery; they're still working on doses, Faden says. Researchers will also need to show that flavopiridol, which was rejected as a cancer drug because of toxicity, is safe in humans as a brain treatment.