Researchers have uncovered a new culprit behind the brain injury suffered by stroke victims. Their new study, published in the Sept. 17 issue of Cell, links brain cell damage to a rise in brain acidity following the oxygen depletion, or ischemia, characteristic of stroke.
The results may lead to new therapies designed to avert the often debilitating effects of stroke, for which successful treatments are currently lacking, the researchers said.
A series of experiments in laboratory dishes and in animals implicates a recently described class of membrane ion channels, called acid-sensing ion channels (ASICs), to the influx of calcium in nerve cells starved of oxygen and subjected to acidic conditions. That calcium overload, long attributed to another group of cellular components, is essential for stroke injury as it sets off a cascade of events toxic to cells, said neurophysiologist and lead author of the study (Zhi-Gang Xiong of Robert S. Dow Neurobiology Laboratories in Portland, Oregon).
What's more, the team reports, rats injected with agents known to block ASICs--including the venom of a tarantula spider--exhibited a reduction in brain damage from ischemia. Mice lacking a functional copy of the ASIC gene were similarly resistant to stroke damage, they found.
"Our study offers multiple lines of evidence that reveal acid-sensing ion channels as major players in the damage suffered by stroke victims," Xiong said. "Furthermore, we found that existing pharmacologic agents that block those channels can dramatically reduce the amount of brain injury."
In the United States, stroke is the leading cause of severe, long-term disability and the third leading cause of death, according to the American Stroke Association. About 700,000 Americans have a stroke each year--one every 45 seconds.
A type of cardiovascular disease, stroke affects arteries of the brain. In ischemic stroke, the most common form, a blood vessel that carries oxygen and nutrients to the brain becomes blocked by a clot. As a result, part of the brain fails to get the oxygen it needs, a condition that damages nerve cells. The effects of a stroke, which can include paralysis and problems with language and vision, depend on several factors including the location of the obstruction and how much brain tissue is affected. The new work identifies a mechanism whereby acidic brain conditions following ischemia spur a portion of the damage.
The normal brain requires complete oxidation of glucose to fulfill its energy requirements, the researchers explained. During ischemia, oxygen depletion forces the brain to obtain energy through anaerobic glycolysis, a process which results in the accumulation of lactic acid. Earlier work indicated that such acidic conditions aggravate ischemic brain injury. However, the group added, the mechanisms had remained unclear.