Portland, Ore.

Researchers discover how small strokes proactively protect the brain against damage caused by larger strokes; discovery may help in development of "brain-protecting" medications.

Collaborative research at Oregon Health & Science University and RS Dow Laboratories at Legacy Health System has uncovered a naturally occurring system in the body that can protect the brain against serious damage during a major stroke. Scientists hope this discovery will aid in the development of medications to protect against serious brain damage in persons at high risk for stroke. The findings will be published in The Lancet and will appear online on Sept. 26.

"This discovery is based on the earlier finding that people who suffer a previous minor stroke have less brain damage during a subsequent major stroke," said Mary Stenzel-Poore, Ph.D., an associate professor of molecular microbiology and immunology in the OHSU School of Medicine.

"What we didn't understand was why this happened. Our research team was able to discover genes affected by smaller strokes, called transient ischemic attacks (TIAs). These changes appear to protect the brain in the case of a future, larger stroke," noted Roger Simon, M.D., director of neurobiology research at Legacy Health System, Portland, Ore.

To conduct this research, scientists first developed a mouse model of stroke. Using this model, they utilized a technique called microarray or gene chip analysis to measure genetic function on a gene-by-gene basis in normal mice compared to mice that have previously had small protective strokes (TIAs). Analysis of these data showed that TIA strokes caused genetic changes that lead to a 70 percent decrease in brain damage during a subsequent larger stroke. These protective genetic changes in the brain were accompanied by decreased blood clotting and a slowdown of the brain's metabolism.

"What's particularly fascinating about these findings is that the changes caused by minor strokes are very similar to the changes that occur in hibernating animals," said Stenzel-Poore. "In other words, a person who has undergone a small stroke may have a lot in common with an animal that's able to slow its metabolism and prevent blood clotting during reduced blood circulation."

While more research is necessary, scientists suggest this finding may help uncover a link to our genetic history. Genetic adaptations once required for hibernation in our animal ancestors now perform another important function - stroke protection.

By better understanding naturally occurring stroke protection, researchers hope medications can be developed to cause similar changes in the body in the absence of a stroke. Such medications would be particularly valuable to at-risk stroke populations such as the elderly. Another population that would benefit from these kinds of medications are coronary bypass patients. Currently half these patients suffer mental decline following surgery. A neuroprotective or "brain-protecting" medication could greatly enhance outcomes for these patients.

Funding for this research was provided by the National Institute of Neurological Disorders and Stroke, a component of the National Institutes of Health.