BOSTON January 23, 2011 Strokes are a leading cause of mortality and adult disability. Those that involve intracerebral hemorrhage (bleeding in the brain) are especially deadly, and there are no effective treatments to control such bleeding. Moreover, diabetes and hyperglycemia (high blood glucose levels) are associated with increases in bleeding during hemorrhagic stroke and worse clinical outcomes.
But Joslin Diabetes Center researchers now have identified one key player that contributes to this increased bleeding, a discovery that may pave the way toward treatments that minimize adverse stroke outcomes both for people with pre-existing diabetes and those with hyperglycemia identified at the time of stroke.
Studies in the lab of Joslin Investigator Edward Feener, Ph.D., pinpointed a new mechanism involving a protein called plasma kallikrein that interferes with the normal clotting process in the brain following blood vessel injury with diabetes. Their work is reported online in the journal Nature Medicine.
The scientists began by injecting a small amount of blood into the brains of rats with diabetes and of control animals without diabetes. The difference was dramaticthe diabetic animals bled over a much greater area of the brain.
Work in the Feener lab had previously implicated plasma kallikrein in diabetic eye complications. When the experimenters pre-treated the diabetic animals with a molecule that inhibits the protein's effects, brain damage from the blood injections dropped to levels similar to that in the control animals. Conversely, when pure plasma kallikrein was injected into the brain, it produced little impact on the control animals but rapidly increased major bleeding in the animals with diabetes.
Further studies by the Joslin researchers showed that normalizing blood glucose levels in diabetic animals could block the effect from plasma kallikrein, and that rapidly inducing hyperglycemia in
|Contact: Eric Bender|
Joslin Diabetes Center