Stroke drug reveals a dark side.

Quick treatment with a clot-busting drug can help prevent some of the damaging consequences of a stroke. However, new research suggests that this modern miracle may come at a price.

A stroke occurs when a blood clot blocks off an artery leading to the brain. Tissue plasminogen activator (tPA), a clot-dissolving substance produced by brain cells -- and manufactured by drug companies -- ordinarily forestalls these clots. When tPA can't handle the job, the clot squeezes off blood flow to parts of the brain.

Studies have shown that stroke patients benefit from the tPA drug if it is given within 3 hours of the onset of symptoms, notes Gregory J. Del Zoppo of the Scripps Research Institute in La Jolla, Calif.

Stuart A. Lipton of Harvard Medical School in Boston and his colleagues decided to study the benefits of the drug for stroke patients by creating the equivalent of a stroke in mice. The researchers temporarily blocked one of two brain arteries in two groups of mice. The first group, genetically engineered not to produce tPA, had less brain damage after the experimental stroke than the second group, which did make tPA. When the researchers injected the synthetic tPA into the brains of mice in the first group, the damaged areas doubled in size. The team describes its results in the February Nature Medicine.

In an accompanying editorial, Del Zoppo questions whether a mouse study bears any relevance to human stroke patients.

Lipton doesn't deny tPA's benefits to humans. He points out that tPA may kill a few brain cells while preserving many more by restoring blood flow. Thus, treatment with tPA still offers human stroke patients a net benefit, he says.

Lipton's team is trying to design a drug that would aggressively dissolve blood clots without killing brain cells. In the meantime, Lipton, a practicing neurologist, still gives his eligible stroke patients tPA.