U of S research reveals how stroke damages brain and offers possible treatment

SASKATOON - University of Saskatchewan researcher Francisco Cayabyab has shed light on a mystery that has long bedeviled stroke researchers: why does brain damage continue hours or days after the initial event?

"When we induce a stroke in animal models, the stroke is happening right at the top of the surface of the brain, the cortex," said Cayabyab assistant professor, Department of Physiology. "What we find is that yes, there is damage in the penumbra (the area immediately around the stroke), but there is also damage deep within the brain."

During a stroke, a blood vessel is blocked, starving brain cells of oxygen and nutrients they need to survive. Cayabyab explained that adenosine, a molecule used in regulating many of the body's functions, is released in response to a stroke and provides protection to the brain in the first minutes after the event. The trouble comes when adenosine levels stay elevated.

Sustained, elevated adenosine levels appear to alter the properties of a class of glutamate receptors called AMPA receptors in brain cells, making them more permeable to calcium. This in turn allows calcium to flood into the cells until it reaches damaging levels. Neurons in the hippocampus, an area of the brain associated with memory, are especially vulnerable. The team's findings were recently published in the Journal of Neuroscience.

"This is quite new," Cayabyab said. "A small ischemic stroke on the surface of the brain can have a global effect, and affect brain regions that are very susceptible to damage such as the hippocampus. This is especially important for people as they get older, since they can have small tiny strokes and an accumulation of these tiny strokes can have a big effect."

The team also developed a peptide, which they dubbed "YD," that appears to lessen or eliminate the effects of adenosine overload, protecting neurons from damage. Another peptide they discovered called "YP" also shows promise.

"This is not just relevant to stroke, but to traumatic brain injury or neurodegenerative diseases like Alzheimer's or Huntington's disease, because we know that as the brain ages, the levels of adenosine increase as well," Cayabyab said.

Cayabyab and his team plan follow-up work to see how the peptides perform when injected at one hour, three hours, four hours post-stroke - the typical window for treating stroke patients with standard drugs such as TPA.

"That's the ultimate goal," Cayabyab said. "Once we show that, I think this is a very good thing to bring up to pharmaceutical companies. It's got a lot of potential."


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Jennifer Thoma

Media Relations

University of Saskatchewan


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