A School of Medicine study, led by neurology professor Katrin Andreasson, suggests that a new treatment for strokes could be realized by focusing on a receptor in nerve and endothelial cells which, when simulated, releases a chemical that helps to dilate blood vessels and improve blood flow. The study, performed on mice, was published last Monday in the online Journal of Clinical Investigation.

The study started by investigating a class of drugs called COX-2-selective inhibitors. Once a spark of promise within the medical community, COX-2 selective inhibitors were believed to have the effects of aspirin without the stomach pain. However, the inhibitors ended up contributing to what it was supposed to prevent: in clinical trials, those taking the drug actually experienced an increased risk of heart attacks and strokes.

The drug functions as a pain reliever by helping to hinder the production of a type of messenger molecule called prostaglandin. Prostaglandins travel from cell to cell, triggering different activities within the cells they land on and bind to. One specific type of prostaglandin, called PGE2, is linked to causing pain and inflammation. In a School of Medicine press release, Andreasson said that her team wanted to see why COX-2-selective inhibitors caused strokes instead of curbing them.

They discovered that PGE2 has four different receptors, and one of these, EP4, causes an increase of nitric oxide, a chemical that helps to relax blood muscles and enhance blood flow, when activated. Mice which were injected with EP4 three hours after a stroke experienced less brain damage.

“We showed that activating this single receptor, EP4, three hours after a stroke not only diminishes the volume of a mouse’s affected brain tissue but also enhances the mouse’s functional recovery,” Andreasson said in the statement. “And we’ve taken this a step further by diligently unraveling the mechanisms by which that happens.”

– Kurt Chirbas