MCG’s neuroscience focus is nourished by research findings that continually
shed new light on the workings of the brain.
For instance, neuroscientist Darrell Brann is probing estrogen’s potential role in reducing stroke damage.
Preliminary data suggest that estrogen and estrogen-like compounds help traumatized cells survive and aid recovery by encouraging certain stem cells to mature into new brain cells, according to Dr. Brann, principal investigator on the $1.7 million five-year grant from the National Institute of Neurological Disorders and Stroke.
The studies target an area surrounding the core of the stroke called the penumbra. “What you have in a stroke is an area deprived of blood flow,” says Dr. Brann. “A lot of cells die because they have no nutrients coming in. The penumbra, on the other hand, has some blood flow, but it is quite diminished.”
And it’s a mixed blessing. While the diminished oxygen levels enable some cells to eke by, they also enable production of free radicals, leftovers of normal metabolic processes that cause cell malfunction and death.
But the oxygen level alone is not to blame. Dr. Brann believes that kinases, enzymes that regulate the activity of proteins by putting phosphates on them, have an important role in the signaling cascade that causes the cells to live or die. “This is a basic mechanism regulating cell signaling and turning off different types of function. We know this process also is involved in cell death related to stroke.” Dr. Brann wants to know how.
“We think free radicals are either turning on some of these kinases or these kinases are inducing the production of free radicals,” he says. “We are trying to figure out that link. Our hypothesis is that free radicals are inducing several of the key death kinases.”
In a stroke animal model, he’s analyzing the activity of known pro-death and pro-life kinases in the brain after a stroke as well as normal levels. And he’s looking at whether estrogen and/or estrogen-like compounds can regulate pro-death and pro-life kinases in a beneficial way after injury.
Estrogen and some of its metabolites have been shown in many systems to be a free-radical scavenger. Dr. Brann’s preliminary studies support this, showing dramatically reduced levels of toxic superoxide, the major free radical, in stroke models treated with estrogen and tamoxifen before stroke. “We know they can do good things in other parts of the body,” says Dr. Brann, “so what can they do to the brain?”
- Toni Baker