Donald Stein, Traumatic Brain Injury Treatment

 


Although most people don't know the difference between a sweet potato and a yam, Donald Stein won't confuse them. Yams, unlike sweet potatoes, naturally produce a hormone called progesterone. Also present in humans and animals, progesterone is a plieotropic hormone—meaning it has multiple actions in the body. Because of Stein's research, one of the things it's doing these days is saving lives.

Stein, a physiological psychologist by training and currently an Asa Griggs Candler Professor in Emergency Medicine at Emory, received his M.A. from Michigan State University and his Ph.D. from the University of Oregon. Before joining the Emory faculty in 1995, he served as Dean of the Graduate School and Associate Provost for Research at Rutgers University. He began his tenure at Emory as Dean of the Graduate School of Arts and Sciences and Vice Provost. He has received many prestigious awards, including three Fulbright Scholarships and a Research Career Development Award from the National Institutes of Health.

After completing his service as Dean and Vice Provost, Stein transitioned to the Department of Emergency Medicine, where he now teaches and conducts research. Although choosing to move from an administrative position to a lab setting is somewhat unconventional, Stein has never looked back. "It turned out to be the right decision for me, given what we've been able to do with our research."

Early in his career, Stein became interested in mechanisms of recovery from brain injury. Digging around in the literature, he found several small, clinical, anecdotal reports concluding that women recover better than men after brain injury. Stein was fascinated, particularly because there was almost no research on why this might be the case. He began running tests in his laboratory and came up with surprising results: female rats had better recovery rates than male rats after traumatic brain injury. "But," says Stein, "it depended on where they were in their estrous cycle at the time the injury occurred." Every five to six days female rats go through their estrous cycle and during this time the levels of progesterone and estrogen vary considerably. Through a series of studies, Stein and his colleagues discovered that estrogen actually did little to shield the brain from traumatic injury. The higher levels of progesterone during the luteal phase of the cycle, on the other hand, had a substantial beneficial impact.

A neurosteroid synthesized in the brain, progesterone reduces swelling after a traumatic head injury. It is produced by males and females, although not in the same quantities. For instance, when a female becomes pregnant, her progesterone increases up to ten times its normal level.

Studies indicate that, for both animals and people, progesterone has extraordinary effects on brain injury patients. In the two human clinical trials that have been conducted (one at Emory and one in China), researchers found an average 50% reduction in the rate of death and significant improvements in functional recovery rates for individuals treated with progesterone compared to those given standard of practice care. It is interesting to note that many of the patients in these studies were males. Equally important is the fact that progesterone seemed to have no adverse effects when given to patients of either sex. Although more clinical trials are being planned, there's reason to believe that the work completed by Stein and his colleagues will be a major breakthrough. Says Stein, "If [progesterone treatment] proves to be fully successful in the multi-center trials, it will likely become the standard of practice of care for trauma patients. The two recent trials with progesterone have been the only ones in over 40 years that were successful."

In addition to having an extremely high safety profile, progesterone is inexpensive, easy to administer, can be used anywhere in the world, and can be extracted from yams without complicated technology. This makes Stein's findings even more remarkable. For example, compared to something like craniotomy or stem-cell therapy to treat a severe traumatic brain injury, says Stein, "all you might need is an alcohol swab, a sterile needle, and some progesterone."

Stein's research has been conducted with a multi-disciplinary group of colleagues from emergency medicine, trauma medicine, neurology, neurosurgery, nursing, and pharmacology. For Stein, working with professionals from different areas has been incredibly rewarding. In his words, "None of this work would have occurred without the successful collaboration of my professional colleagues, especially Drs. David Wright, Arthur Kellermann, and the other physicians in emergency medicine here at Emory." He also credits undergraduate, graduate, and post-doctoral students with shouldering much of burden in the lab, and emphasizes that the advances made in his lab would not have been possible without their contribution: "None of the work would ever get where it is today without all these people. This is really a tremendous team effort."

Mentoring students is an aspect of his job that Stein particularly enjoys. He comments, "We have had outstanding undergraduates from the neuroscience program…It's just a great experience for us to have them in the lab. They have been helpful, they have published with us, they have gone on to be very successful." In addition to mentoring students, Stein teaches a number of courses and seminars at the undergraduate and graduate levels. In both his teaching and research, he is able to see a direct link between his efforts and a contribution to the public good—something he finds gratifying.

Over the years, Stein has met with many hurdles. The research itself has always been challenging. But, says Stein, "even harder was to convince people this wasn't some fool's errand. That it really had some value." Although he met much resistance, Stein feels fortunate that he has always been able to count on the love and support of his wife, Darel. At Emory, he has also found a group of dedicated colleagues who have encouraged him to believe in his work.

In the future, he hopes to collaborate with this team to continue new research on progesterone, exploring its effectiveness in treating stroke, pediatric and cardio-vascular injuries, and neuro-degenerative disorders and peripheral nerve injuries. Although he considered retirement at one point, these days he is far too immersed in the lab and in promoting the clinical trials to walk away. Says Stein, "It's just an amazing, exciting field."