Autumn 2008

Cell Guard

Following traumatic brain injuries, progesterone may cushion the blow

By Mary J. Loftus

A bike accident, a sports injury, falling off a ladder, an improvised explosive device beside a war-torn roadway—a traumatic brain injury can occur in hundreds of different ways. And, ironically, the body’s response to such an injury actually does further damage, resulting in brain swelling and the death of additional brain cells.

At least 5.3 million Americans—about 2 percent of the population—live with disabilities from brain injuries, according to the Brain Trauma Foundation. About 1.5 to 2 million more receive brain injuries each year, which are major causes of death and disability among children and military personnel.

Despite the widespread impact, no effective medical treatments had been developed for traumatic brain injuries for nearly three decades—until now. Emory researchers discovered that giving progesterone to trauma victims shortly following the injury can help to reduce the risk of death and the degree of disability.

Researchers designed a three-year pilot study called ProTECT (Progesterone for Traumatic brain injury-Experimental Clinical Treatment). Results showed that progesterone given soon after the brain injury is safe, appears to cut the risk of death by 50 percent, and reduces subsequent disability.

David Wright, assistant professor in the Department of Emergency Medicine and the study’s lead author, says there is now hope of an effective treatment for traumatic brain injuries—and possibly other neurological injuries such as strokes, spinal cord injuries, and multiple sclerosis.

Neurobiologist Donald Stein, Asa G. Candler Professor of Emergency Medicine, who has been studying progesterone for nearly twenty years, first discovered its neuroprotective properties in his lab. “Our research found that male and female rats with brain injury developed less brain swelling and recovered more completely when they were treated with progesterone shortly following the injury,” Stein says. “The hormone seems to slow or block damaging chemicals that are released after a brain injury, protecting the brain from the death of brain cells.”

Stein recently was named by Ladies’ Home Journal as one of four winners of the Health Breakthrough Award for 2008 for his work with progesterone and brain injuries.

Although widely considered a sex steroid, progesterone is also a neurosteroid present in small amounts in the brains of both males and females. Studies suggest that progesterone is critical for the normal development of neurons in the brain and has a protective effect on damaged tissue.

Study participants were enrolled at Grady Memorial Hospital’s Level 1 Trauma Center. To be a candidate, patients had to reach the hospital within eleven hours of injury and have experienced a “blunt” traumatic brain injury (typically from a car accident, motorcycle crash, or fall).

For 2009, the research team is planning a large, NIH-sponsored, multicenter clinical trial designed to test the effectiveness of progesterone in 1,140 patients with traumatic brain injuries. They also plan to study the effects of progesterone in treating ischemic stroke, blast-related brain injury, and pediatric brain injury.