New stroke treatment could help prevent brain damage

Researchers at the University of Missouri have shown that a new compound could be effective in protecting the brain from damage in the crucial hours after a stroke.

Stroke is the fourth leading cause of death in the U.S., with more than 800,000 cases each year. The most common form is the ischemic stroke, when a blood clot blocks flow to the brain. Not only does brain tissue start to die from the lack of oxygen and nutrients, so do blood vessels behind the clot.

Only one treatment is available to limit the brain damage from stroke a clot-busting drug called tissue plasminogen activator, or tPA, which must be given within the first three hours of a stroke's onset. While this drug can restore blood flow to the brain, it also carries a significant risk of causing the weakened blood vessels to break apart, sending blood into nearby brain tissue and causing deadly swelling.

By mimicking a stroke in mice, MU researchers have helped discover that targeting an enzyme which plays a role in the breakdown of blood vessels can prevent bleeding in the brain. The findings were published recently in the journal Molecular Neurodegeneraton.

"While we are still in the research phase for this type of compound, we believe it could be combined with tPA in the future to buy ischemic stroke patients a longer window of time to receive emergency treatment," said Dr. Zezong Gu, assistant professor of pathology and anatomical science at the MU School of Medicine.

A group of more than 20 matrix metalloproteinase enzymes are known to contribute to the degeneration of the brain after stroke and traumatic brain injury, particularly one enzyme known as MMP-9. Researchers at the University of Notre Dame developed a compound, known as a gelatinase selective inhibitor, which only targets MMP-9.

At the MU medical school's Center for Translational Neuroscience, scientists have also been studying how to inhibit MMP-9 by inducing a blood clot in the brains of mice, one of the few labs in the country able to successfully produce an ischemic stroke in an animal model. The two universities were able to team up for the latest study.

"To be able to study the effectiveness of this potential new treatment under these conditions provides us with a highly unique set of data showing this compound can disrupt key harmful pathological events that occur after stroke," said Dr. Jiankun Cui, the study's lead researcher at MU.

The mice were injected with the inhibitor within two and four hours after the stroke, as well as continuously for the next week. Researchers found it significantly reduced brain damage and the amount of bleeding. Further tests are in the works.

"With this compound we've now confirmed a potential method to rescue the blood vessels from the damaging effects of MMP-9 and protect neurons at the same time," Gu said.

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New stroke treatment could help prevent brain damage