"Preconditioning" Helps Protect Brain's Blood Vessels from Stroke

Challenging brain tissue with a small noxious stimulus beforehand gives it a resilience that can lessen damage to blood vessels during a stroke, report researchers at Weill Cornell Medical College in New York City.

"This preconditioning works along the theory of 'what doesn't kill me makes me stronger,'" explains senior researcher Dr. Costantino Iadecola, the George C. Cotzias distinguished professor of neurology and neuroscience and Director of Neurobiology at Weill Cornell, and attending neurologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

"We already knew that preconditioning helps minimize damage to heart tissue — it's a strategy cardiologists routinely use today. And we know it can help protect brain cells — neurons — against stroke damage," Dr. Iadecola says. "Now, besides illuminating mechanisms involved in this process, our new study in mice demonstrates that preconditioning also shields the brain's blood vessels from stroke injury," he explains.

"The hope is that by studying this natural means of self-defense, we might develop potent pharmaceutical means of either preventing stroke or minimizing stroke damage," he says.

The findings appear as a special highlighted paper in the Journal of Neuroscience.

According to the National Stroke Association, stroke is the third leading killer of Americans and the number one cause of adult disability. And yet scientists have still not developed a truly effective means of treating these attacks.

"We knew that preconditioning — giving the brain a slight noxious stimulus beforehand — can strengthen brain cells against damage from a larger insult later on. This phenomenon occurs naturally in the human brain," explains lead researcher Dr. Alexander Kunz of the University of Dresden, Germany. Dr. Kunz worked on the study while at Weill Cornell.

But exactly how does preconditioning work, and can it come to the aid of the brain's vasculature, as well?

Based on their prior work, the researchers knew that the protective effect of preconditioning relies on a ubiquitous chemical in the blood called nitric oxide (NO). Injuries to tissues — such as the ischemia that occurs in stroke — activate certain enzymes that produce NO. This process also produces destructive, oxidative byproducts called free radicals.

According to the new study, NO combines with these free radicals to produce low levels of another molecule, called peroxynitrite.

"At higher levels, peroxynitrite is a very dangerous chemical for tissues," Dr. Iadecola explains. "But we discovered that at these lower concentrations, it's actually beneficial — helping to preserve the function of blood vessels in the brain whenever a more toxic event occurs."

Normal mice given an inflammatory toxin called lipopolysaccharide (LPS) 24 hours before an induced stroke — the preconditioning method used in this study — had a 68 percent reduction in stroke intensity, the researchers found.