NIH grants $221,250 to OU-HCOM ischemic stroke research 

Dr. Yang Li will use funds to investigate the role of zinc in cell death

October 15, 2009

Yang Li, M.D. (equiv.), Ph.D., associate professor of biomedical sciences, was recently awarded $221,250 from the National Institutes of Health to continue his research on “Elevated zinc in ischemia and reperfusion.”

Dr. Li’s study follows his previous discovery of elevated levels of zinc in cells before their death following hypoxic-ischemic brain injury. This type of injury to cells in the brain and spinal cord is the result of a lack of oxygen and lack of blood flow to the brain—which can cause strokes.

The role of zinc ions in strokes is still largely unknown, and that is what Li and his team hope to determine with the help of this grant. Discovering which particles are present and active during cell death could be instrumental in developing new pharmaceutical treatments for ischemic strokes, which have a very narrow treatment time frame.

Li’s suggestion that zinc could be involved in a pathway that leads to cell death and, by extension, brain damage following ischemic strokes, may refute the current theory that calcium is responsible for ischemic strokes.

The presence of calcium in cells and a calcium-centered approach to study strokes has been established for years, but Li noticed that the indicators used to detect calcium in cells also report elevated zinc levels during cell death. However, until recently, large levels of zinc could not be confirmed in cells, leading most scientists to disregard the overlap of zinc and calcium in these indicators.

Li argues that cellular zinc levels appear to be low or missing from normal cells because zinc ions bind so tightly to cell proteins that they evade detection. They appear to rise sharply before and during cell death because, according to Li, cell stress responses immediately following stroke triggers the “hidden” zinc to emerge, which facilitates brain injury.

New indicators have been developed that can determine the presence of zinc without detecting calcium. Using these, Li has confirmed physical evidence of zinc levels in the cells.

Although Li is not certain that calcium is at all involved in ischemic stroke, some scientists are hesitant to disregard that idea, he says, adding that researchers are now looking for a new theory of ischemic stroke that involves both zinc and calcium.

Li remains confident in his findings, and he is proud that his research helps others explore options beyond the traditional calcium-centered approach, which has so far not yielded any successful clinical trials.

“We have demonstrated that these so-called calcium indicators perceive zinc under given experimental conditions—with higher zinc sensitivity,” he says. “But now we need to capitalize on the findings and to clarify the role of zinc in stroke research.” The important thing, he added, is considering new ideas.