However, an accompanying journal editorial suggests that the implications of the findings for human health remain unclear. And in a statement, officials from the American Heart Association say it would be "terribly unfortunate if an appropriate stroke patient were not given a clinically proven medication due to this preliminary finding in mice."

Previous research has shown that tPA, administered within three hours after a stroke, can save lives, limit the severity of brain damage, and increase long-term survival odds.

But researchers at Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts, contend that "(post-stroke) therapeutic intervention with tPA in the nervous system may represent a two-edged sword."

They induced artificial strokes in the cerebral arteries of two types of mice. One group were specially bred to lack tPA, which also occurs naturally within mammalian brain tissue. The other group consisted of normal, tPA-bearing mice.

After their artificially induced strokes, each of the mice were administered therapeutic tPA at levels correlating with standard human dosages.

The researchers discovered that the presence of "tPA dramatically increased the size of cerebral infarction (damaged brain tissue)."

They say further examination of mouse brain tissue after stroke and subsequent tPA treatment also demonstrated that those mice without natural tPA suffered less neural damage than their tPA-bearing kin.

The Boston researchers believe their findings indicate "that tPA can increase stroke-induced injury."

In his editorial, Dr. Gregory Del Zoppo of the Scripps Research Institute in La Jolla, California, called the findings "provocative." However, he notes that "clear differences between rodent and primate central nervous systems" could undermine any implications for human health from the study.

Del Zoppo also pointed to a previous study in baboons, which revealed that the primate's brains suffered no noticeable increase in stroke-related tissue damage as tPA dosages rose.

He says that, despite the findings of the Boston study, it is still difficult to conclude that tPA "is likely to increase ischemic (stroke) brain injury in human stroke victims."

The American Heart Association (AHA) statement notes that tPA is the only approved clot-dissolving drug for ischemic stroke. The organization agrees that additional research is needed to improve drug therapy for stroke, "...but patients should continue to get tPA based on its established clinical benefit."

In the US, stroke is the third leading cause of death and the number one cause of major disability in adults.

January 28, 98
SOURCE: Nature Medicine