You can have too much of a good thing, it seems—at least when it comes to physiotherapy after a stroke. Many doctors believe that it is the key to recovery: exercising a partially paralyzed limb can help the brain "rewire" itself and replace neural connections destroyed by a clot in the brain.

But the latest animal experiments suggest that too much exercise too soon after a brain injury can make the damage worse. "It's something that clinicians are not aware of," says Timothy Schallert of the University at Austin, who led the research.

In some trials, stroke victims asked to put their good arm in a sling—to force them to use their partially paralyzed limb—had made much better recoveries than those who used their good arm. But these patients were treated many months after their strokes. Earlier intervention, Schallert reasoned, should lead to even more dramatic improvements.

To test this theory, Schallert and his colleagues placed tiny casts on the good forelimbs of rats for two weeks immediately after they were given a small brain injury that partially paralyzed one forelimb. Several weeks later, the researchers were astonished to find that brain tissue surrounding the original injury had also died. "The size of the injury doubled. It's a very dramatic effect." says Schallert.

Brain-injured rats that were not forced to overuse their partially paralyzed limbs showed no similar damage, and the casts did not cause a dramatic loss of brain tissue in animals that had not already suffered minor brain damage. In subsequent experiments, the researchers have found that the critical period for exercise-induced damage in rats is the first week after the initial brain injury.

The spreading brain damage witnessed by Schallert's team was probably caused by the release of glutamate, a neurotransmitter, from brain cells stimulated during limb movement. At high doses, glutamate is toxic even to healthy nerve cells. And Schallert believes that a brain injury makes neighboring cells unusually susceptible to the neurotransmitter's toxic effects.

Randolph Nudo of the University of Texas Health Science Center at Houston, who studies brain injury in primates, agrees that glutamate is the most likely culprit. In experiments with squirrel monkeys suffering from stroke-like damage, Nudo tried beginning rehabilitation within five days of injury. Although the treatment was beneficial in the long run, Nudo noticed an initial worsening of the paralysis that might also have been due to brain damage brought on by exercise.

Schallert stresses that mild exercise is likely to be beneficial however soon it begins. He adds that it is unclear whether human victims of strokes, like brain-injured rats, could make their problems worse by exercising too vigorously, too soon.

Some clinics do encourage patients to begin physiotherapy within a few weeks of suffering a traumatic head injury or stroke, says David Hovda, director of brain injury research at the University of California, Los Angeles. But even if humans do have a similar period of vulnerability to rats, he speculates that it might be possible to use drugs to block the effects of glutamate.