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."

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."

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