Sex Hormones Heal Injured Brains: Why Research Matters

Basic research on rats may help millions recover from trauma.

Posted Dec 29, 2011

I was sipping eggnog the other day, chatting with my sister while the kids opened presents.  She produces press releases and videos for Emory Medical School. I teach developmental psychology and statistics at Oberlin.

We were talking about how hard it is for scientists to work with the media when she started telling me about this scientist who had been working for years doing basic research on brain injury in rats. Forty years ago, he had started to notice that the female rats were healing much faster than the male ones.  And that led to . . .

"Progesterone treatment for traumatic brain injury," I said.

"How did you know?"

"It's the chi-square question that I use on the statistics final.  People treated with progesterone during the first hours after a traumatic brain injury are 1/3 as likely to die in the first 30 days.  I read it a few years ago in the New York Times."  I remembered reading the article clearly.  I had been reading the paper over breakfast, and it was such a simple, clean study that I knew my intro students would be able to work through the stats on their own.

"Yeah," she said.  "And it turns out it works for all sorts of brain injuries—not just car accidients.  Surgery, strokes, and brain lesions, too."

We started laughing.  The example I had chosen for a statistics question given in an exam in Ohio, pulled from the New York Times, was based on a press release written by my sister in Atlanta, Georgia. 

Sometimes odd coincidences come together with surprising consequences.

And, in fact, that's the story behind traumatic brain injury and progesterone.

A hidden epidemic

Remember the kids you knew in high school who had that horrible car accident - two died and the other in a coma?  Or the colleague who was rushing to a meeting, crossed the meridien strip, hit a truck, spent a year in the hospital, and is still in rehab?  Or the football player who never fully recovered from that tackle that just went wrong?  Traumatic brain injury.

Brain trauma is the hidden war injury from Iraq and Afghanistan. Those wonderful helmets that protect servicemen from explosions both keep veterans alive who would have died in earlier wars, and also funnel the blast into the delicate tissues of the brain. Some of those injuries are obvious: paralysis, speech impediments, or a sudden inability to read. But many others are subtle and harder to detect: inability to control anger, loss of concentration, or difficulty learning new material.

Brain injuries are common, devastating, and hard to treat. According to Emory University's project PROTECT:

  • A US citizen sustains a brain injury every five seconds. 
  • Between 1.5-2 MILLION Americans are permanently disabled from a TBI every year.
  • The Center for Disease Control estimates that brain injuries cost the us 60 BILLION dollars a year in lost productivity.

In the past year, three of my students have suffered silly, simple accidents - walking into a light pole, falling off a bike, a funny bump playing basketball - that have resulted in concussions serious enough that they had trouble finishing out the semester.  Brain trauma is all around us.

The Estrus Cycle of Rats

Dr. Donald Stein began working with traumatic brain injury patients in the early 70's. There was anecdotal evidence that women were recovering better than men. But, during the height of the feminist movement, few people wanted to look for brain differences in men and women. 

But he persisted. Systematic work with rats documented the difference, but it was, as most things are, more complicated than a simple difference between male and female. Female rats' ability to heal depends on where they are in their estrus cycle: it was hormone dependent. When female rats were injured when their progestorone peaked, their recovery was much better. 

Describing his colleagues reactions when he injected brain injured MALE rats with progesterone, he says:

"They thought, ‘Are you nuts? You're going to give this female hormone to male rats and see what happens?"
Again, he persisted. And he was right. When injected with progesterone, swelling in the brains of injured rats the brain was reduced and the males healed as well as the females. More importantly than how their brains looked, was how they healed. Cognitive impairment was markedly reduced.  A breakthrough!

From Lab to Emergency Room

Although we typically think of progesterone as a female sex hormone, it is present in both males and females. It is also, present in small quantities in the brain. And the brain, it turns out, is nested with progesterone recepters.

Learning of Stein's work with brain injury in rats, emergency room physician, David Wright, decided a begin a clinical trial of progesterone to see if it helped real patients in real time.

Progesterone has several qualities that makes it a good candidate for a clinical trial.  First, it's a naturally occurring hormone in humans. It's also been studied pharmaceutically as a major component of birth control pills. It can also be easily measured in the blood and—miracle of miracles—it's even cheap. 

Not only that, but it works. 

In an initial study of the effects of progesterone in 100 patients, 40 percent of those given the placebo died within 30 days, compared with 13 percent who received progesterone.  Not bad for an initial test.  And the first major breakthrough in the treatment of traumatic brain injury in 30 years.

Basic Science, Applied Research and Making the Right Connections

It is easy for politicians to make cheap shots at scientists by scornfully reading from the summaries of our grants. Don't all these projects sound stupid?

But results like these are why the government funds basic research. You never know when a chance observation—female rats heal better than males after brain injuries—will lead to a breakthrough.

But put the right observations, an understanding of a previously misunderstood phenomenon, and the right people together—a basic researcher and an EMT doctor—and suddenly we have the potential for THOUSANDS—maybe millions—of people to walk and talk and function fully again.

And coincidences like that happen all the time.

Just like my sister and I coming together over eggnog and finding a connection between her work at Emory and my statistics class at Oberlin.

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(c) Nancy Darling, 2011.  All rights reserved.


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