A Chink in the Brain's Defenses

The blood-brain barrier, a bastion against harmful chemicals and microbes, may be a lot more permeable than researchers have thought. Scientists have found that in mice, at least, the barrier weakens during emotional stress.

The blood-brain barrier is a layer of tightly packed endothelial cells and connective cells called astrocytes that strictly regulates the flow of chemicals in and out of the brain. Researchers at Hebrew University in Jerusalem and the Israeli Defense Force's Medical Corps have found that a variety of chemicals penetrate the mouse blood-brain barrier much more readily when the mice are forced to tread water, a condition that induces stress. For instance, Evan's blue, a dye that stains the cellular protein albumin, penetrates the brain 10 times more efficiently in stressed mice than in unstressed mice. According to the report, in the December issue of Nature Medicine, increased blood flow in the stressed mice would account for only a fraction of the increase in permeability.

"It's intriguing," says Rajesh Kalaria, a neurologist at Case Western Reserve University in Cleveland. Scientists have noted that the blood-brain barrier is weakened in some diseases such as epilepsy or in cases of dementia, he says, but the stress findings are novel.

The study was spurred by findings in Gulf War veterans suggesting that they had suffered short-term neurological problems, such as insomnia and nervousness, after taking the anti-nerve-gas agent pyridostigmine. According to Hermona Soreq, the head of Hebrew University's Institute of Life Sciences and a study author, the mouse studies show that "Pyridostigmine penetrates the brain rather effectively under stress conditions." But Soreq says that the study was not aimed at probing the nature of Gulf War syndrome.

The findings raise questions about the proper dosage of drugs that target the brain. "When you're under stress, drugs can have greater potency," says Kalaria. Stress, he says, "may compound the effect" of psychoactive drugs.