Emory Report

October 25, 1999

 Volume 52, No. 9

Stein links hormones to brain trauma treatment, recovery

Reasearchers at Emory say they have evidence that the female brain may be better able to repair itself following injury than the male brain, a finding that could lead to new treatments for traumatic brain injury.

Donald Stein, a neuroscientist at Emory and dean of the graduate school, reports he has amassed intriguing evidence that the changing cycle of circulating estrogens and progesterones affects the outcome of brain repair. Women naturally have higher levels of both of these hormones.

To test his theory, Stein and his colleagues stimulated the cervix in female rats so that the animals entered a luteal phase--the hormone progeterone at high levels and estrogen low levels. When estrogen was high, the animals had lots of symptoms following brain injury. But when progesterone was high, the symptoms of the same type of injury were not present.

When he examined the cerebral ventricles of the brain in male and female rats, he found that animals low in progesterone showed swelling and increased cranial pressure. But when animals were high in progesterone, the ventricles were normal.

"Cerebral edema, or swelling, is what causes most death," said Stein. "In all of the studies, the males always had worse edema than the females." Each year, 2 million people in the United States suffer from brain trauma.

Stein's studies suggest progesterone plays an active, reparative role in the brain, and he believes it may be possible to use progesterone to protect the brain following such injury.

In the animal studies, progesterone injections given to both males and females right after the injury prevented cerebral edema, or brain swelling. The earlier the progesterone was given, the better the protection. Even when the hormone injection was given 24 hours later, there still were some signs of protection, Stein said. But by 48 hours, the protective effects disappeared.

Researchers at the Henry Ford Hospital in Detroit also found that progesterone offered protection in male and female rats experiencing the equivalent of a stroke.

Stein and a growing number of others suspect that progesterone is neuroprotective and a powerful immune system modulator, which might explain why it remains so high during pregnancy. While the ovaries are a main source of estrogen and progesterone, Stein said progesterone also is manufactured by glial cells in the brain--support cells that nourish neurons.

There is a growing collection of human studies that support his theory.

Epidemiologists have found that stroke victims who have yet to go through menopause have better recoveries than post-menopausal women and men (men make much less progesterone than women.) Once a woman hits menopause, these protective effects disappear.

Also, Rubie Senie, an epidemiologist at Memorial Sloan-Kettering Cancer Center in Manhattan, has shown that breast cancer patients did better-both with regard to recurrence of cancer in remaining breast and to the risk of dying--if they had undergone surgery during the time in their menstrual cycle when progesterone was high. The higher the progesterone, the better the recovery process.

Now, the neuroscientist hopes to figure out why progesterone is so beneficial in the brain. He suspects it reduces water content in the brain, and thus prevents swelling. His team is completing an epidemiological study at three hospitals to compare recovery from brain injury between men and women.

"Progesterone injections may be an inexpensive and safe way to provide brain protection," Stein said. He conducted an extensive search of the literature and found only one downside of progesterone injections: It enhances the effects of cocaine in people who abuse the illegal stimulant. Some doctors are now even experimenting with progesterone treatments in women who have epileptic seizures during a specific phase in their menstrual cycle when estrogen is high. (Stein doesn't think estrogen has a harming effect, but that progesterone has a strong protective effect, he stressed.) Other researchers have published evidence that progesterone has antioxidant effects and could be working through this mechanism to prevent tissue breakdown.

"This is very interesting," said Rolland S. Parker, a neuropsychologist at New York Medical College and president of the New York Academy of Traumatic Brain Injury. Parkers' own studies suggest there are many symptoms of the mild brain injury that go undiagnosed, including pain and other cognitive deficits.

This article first appeared in Newsday and is reprinted with permission.

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