Discovery changes ideas about damage from strokes

lp the brain. Other effects of PGE2, such as anti-inflammatory effects, may also contribute to its protective abilities in the brain, says Andreasson.

"We think that COX-2 products that increase cyclic-AMP may prove to be protective, like PGE2, while those that lower cyclic-AMP may contribute to COX-2's known negative effects on brain damage from stroke," she says. "We're still working on it."

About 4 million Americans are currently living with the effects of stroke, in which blood flow and oxygen delivery to the brain are interrupted by blockage or breakage of a blood vessel. At first, brain cells are shocked, not killed, but their chances of recovery decrease rapidly as time passes.

If given within an hour of the stroke, a drug called t-PA can prevent extensive damage by dissolving the blood clot that caused the stroke. However, finding a way to intervene later on -- for patients whose symptoms aren't immediately recognized or who are more than an hour from a hospital -- could dramatically improve recovery and reduce the financial burden of strokes, which the National Stroke Association estimates is roughly $43 billion per year in the United States.

"We still need to determine whether stimulating the PGE2 receptor hours after a stroke can protect mice from damage," says Andreasson, who is conducting some of those studies now. "If so, pursuing this prostaglandin as a potential clinical target will be of great importance."

COX-2 has a significant role in brain damage after stroke in mice, and Andreasson has been searching for how exactly COX-2 causes damage. Scientists know that COX-2 is involved in creating inflammation, or swelling (drugs like Celebrex and Vioxx inhibit COX-2 and are widely prescribed for arthritis and other inflammatory conditions), but its activity leads to the production of a number of different molecules which could be more directly responsible for its effects. Andreasson and her colle

Contact: Joanna Downer
Johns Hopkins Medical Institutions

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