Protecting the Brain with Progesterone

May 29, 2007— -- Traumatic brain injury, also called TBI, has become the signature injury of the war in Iraq -- an alarming realization, given that many doctors feel effective treatment for brain injury is currently lacking.

But doctors at Emory University are hopeful that they may have uncovered the next revolution in TBI treatment.

In a small, preliminary study of 100 patients published recently in the Annals of Emergency Medicine, doctors gave brain injury patients high intravenous doses of the pregnancy hormone progesterone within 12 hours of injury.

Patients who received the hormone cut their risk of dying by 57 percent.

The study "gives hope where there has been no hope before," said the the study's lead author, Dr. David Wright, an assistant professor in the department of emergency medicine at Emory.

And despite being given very high progesterone levels -- three times higher than what is found in normal pregnancy -- study patients had no serious progesterone-related side effects, demonstrating that such a treatment would likely be safe.

Donald Stein, professor in emergency medicine at Emory University and principal investigator of the trial, added that in terms of TBI, the study represents "the first successful clinical trial in 40 years; it could mean a breakthrough in treatment."

Progesterone May Protect Brain

While progesterone is most often thought of as a pregnancy-related hormone, it really is a hormone made by the brain, for the brain.

In fact, it turns out that progesterone is vital for brain cells -- which may explain why progesterone levels are so high during pregnancy. Researchers suggest it could protect the fetus during the critical time of brain cell maturation.

"Repairing the brain and spinal cord after injury is very similar to pregnancy," Stein said. "You have to grow new neurons."

Such a feat was once thought to be impossible, as most scientists believed the brain to be incapable of repairing itself after injury. Wright said that until now, all doctors could do was to "prevent swelling and keep patients alive until the brain recovers itself."

And in this case, early intervention may be crucial. Doctors now regard the initial bruise to the brain as just the beginning of the problem for TBI patients.

"The initial event only contributes to 25 percent of the injury; it is the neurotoxic cascade that happens after bruising that contributes to most of the injury," Wright said.

During this "cascade," a floodgate of neurochemicals opens into the brain, overwhelming brain cells and eventually killing them through "cell suicide."

When this happens, the size and seriousness of the injury to the brain can quickly grow.

"The original injury may be the size of a quarter, but after the neurotoxic cascade it becomes the size of a baseball," Wright said.

The researchers believe progesterone shuts down this cascade, preventing brain damage by decreasing cell suicide and brain swelling.

And the sooner progesterone is given, the better. Less than two to four hours is ideal, but beneficial effects have been seen up to 24 hours after injury.

Stein said progesterone "has the best window of treatment opportunity -- better than any other agent that has been tested."

Progesterone in Wartime

The exact number of traumatic brain injuries among troops wounded by improvised explosive devices, or IEDs, is difficult to estimate.

According to the Department of Defense's Deployment Health Clinical Center, nearly one out of every three injured troops seen at Walter Reed Medical Center from 2003 to 2005 had a traumatic brain injury.

The advances in armor technology, vests and helmets have prevented a lot of previously lethal penetrating brain injuries. But instead of dying, soldiers are now commonly faced with brain injury.

"We can stop the bullet, but we can't stop the concussive wave," Wright said. "Brain injury is now going to be the predominant type of injury."

In combat zones, there is currently no treatment at all available for concussive or blast injuries. Wright envisions a day when progesterone would be included in war kits. Soldiers and medics "could inject progesterone in the field immediately after injury," Wright said.

Brain Injury at Home

TBI is not just a war zone phenomenon. Traumatic brain injuries happen every day in the United States, most commonly after car accidents and falls.

According to the Centers for Disease Control and Prevention, 1.4 million Americans suffer brain injuries each year, and 50,000 die as a result.

Surviving a traumatic brain injury means a higher risk of developing other neurological disorders, including Alzheimer's disease and Parkinson's disease, and difficulties with memory, language and emotion.

If progesterone proves to be successful in larger TBI trials, Wright advocates paramedics' use of progesterone by injecting it into patients who are being transported in ambulances. Injecting progesterone at the scene of an accident, even while patients are trapped in cars, could make a huge difference, Wright said.

Not Yet Ready for Battle

Progesterone for brain injury does have its skeptics. Dr. Alex Valadka, vice chair of neurosurgery at the University of Texas Medical School at Houston, said he won't give progesterone to his brain injury patients just yet.

"There is a good chance that in four or five years we could find out this is a bust," he said.

Though the prospect of progesterone for the brain may be exciting, this is the first human study with a suggestion of benefit. Researchers agree further studies are necessary, and multicenter trials could be under way as early as next spring.

But this research may give hope to the millions of people who face traumatic brain injury at home and at war.

"In over 30 years, there has not been a good treatment for head injury," Wright said. "There is currently nothing. We finally have something that may work for these patients."