$221,250 to OU-COM 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
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.