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Enzyme causes brain blood vessels to enlarge during injury, UI study shows

IOWA CITY, Iowa -- An enzyme notorious for making a bad situation worse when it comes to inflammation causes the brain's blood vessels to dilate when the brain becomes injured, a University of Iowa study revealed.

In the recent study, Eddie Brian, M.D., UI associate professor of anesthesia, found that when exposed to inflammatory stimuli, the brain in a rat model expressed the enzyme cyclooxygenase-2 (COX-2), which led the brain's blood vessels to dilate.

Learning about brain inflammation is important because the effects from inflammation often cause more damage than the initial injury itself, Brian said. All brain injuries -- including stroke, head injury, cerebral ischemia, infection (meningitis), HIV dementia and multiple sclerosis -- have an inflammatory component.

"Dilation of brain blood vessels during brain inflammation may have an important deleterious effect, as the brain is normally very dependent on its highly regulated blood flow," Brian said. "During inflammation, if brain blood vessels dilate, then blood flow can become maldistributed in the brain, leading to ischemia or brain damage."

COX-2, which researchers discovered only this decade, is an important inflammatory mechanism and plays a role in other conditions such as arthritis. Under normal conditions, cells do not express COX-2. However, when injury or inflammation occur, COX-2 kicks in and produces inflammatory compounds from precursors that exist in all cells. These compounds lead to increased inflammation.

Before investigators can develop therapy to combat COX-2 in the brain, they must first understand what causes the brain to express the enzyme when the brain becomes injured. Brian plans to continue his investigation in that area and hopes to probe more extensively into how COX-2 affects other aspects of the brain and injury.

"Understanding inflammation in the brain may lead to therapy to limit inflammation and limit secondary brain damage," Brian said.

The other UI investigators involved in Brian's research included Steven A. Moore, M.D., professor of pathology, and Frank M. Faraci, Ph.D., associate professor of internal medicine and pharmacology.

Brian's work appeared in the December issue of Stroke.

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