Method probes chemistry of stroke, aging.

A technique used to measure fats and proteins in food products may now help scientists detect chemical changes in the brain that occur with stroke and aging, a group of researchers reports.

Robert A. Lodder and his co-workers at the University of Kentucky Medical Center in Lexington have found that, in gerbils, near-infrared light can penetrate the skull to reveal the degree of tissue oxidation -- the chemical damage to fats and proteins -- in the brain.

"We actually get the scans through the skull, the hair, and the brain and get chemical information back," says Lodder. But some scientists express skepticism about applying the work to humans.

The technique, called near-infrared spectrophotometry, gives researchers a non-invasive tool for probing the chemistry of living systems. While magnetic resonance imaging (MRI) and CAT scans provide excellent views of anatomical structure, they reveal little about molecular structures. Hospitals use near-IR spectrophotometric devices to monitor the oxygen-carrying state of hemoglobin in the blood of newborns suffering respiratory distress, and health clubs use the technique to estimate patrons' body fat. The Kentucky group, however, is the first to adapt the method for stroke and aging research, Lodder says.

The team shines a beam of near-IR light onto the head of an anesthetized gerbil. A spectrophotometer measures the amount of light, in wavelengths from 1,100 to 2,500 nanometers, transmitted through the brain. A supercomputer then analyzes the data and cranks out a graph showing the amounts and types of fats and proteins. After a stroke or with increasing age, the lipid signals shift to longer wavelengths, the group reports in the May 15 issue of ANALYTICAL CHEMISTRY. This observation suggests that unsaturated fatty acids convert -- by oxidation -- to saturated ones, or else switch the configuration of the molecule from the cis to the trans form.

Using the near-IR analytical method, Lodder's team found that these damaging changes, when spurred by a stroke, take place well after the initial clot prevents oxygen from reaching the tissue. They studied the near-IR scans of three gerbils given deliberate 10-minute strokes and found that oxidative damage began at least four hours after circulation was restored. By then, reactive chemicals called free radicals, which build up in the oxygen-starved area, would have begun attacking nearby tissues, the researchers believe.

Normal mammalian metabolism generates smaller quantities of free radicals, resulting in similar brain tissue damage that accumulates with age, Lodder says. His group could discern no difference in the near-IR scans of a young adult gerbil subjected to 10 minutes of stroke and an aged one that had a 5-minute stroke. "It looks like stroke is just an accelerated aging process, at least according to this near-IR test," he says.

Lodder's group is using near-IR to gauge the effectiveness of free-radical-quenching drugs that could potentially treat stroke and diseases of aging. The new technique reduces the number of animals needed for such studies, he notes. Because the method also detects water, the team hopes to adapt it to evaluate edema in humans, including by concussion.

Biophysicist Britton Chance of the University of Pennsylvania in Philadelphia says, "This paper calls attention to the great potential of red-light spectroscopy of tissues. But evaluation of edema is more important than the changes of brain fats, and penetration deeper than 4 millimeters will be necessary for application to the human brain."

Karl Norris of Beltsville, Md., who developed the fat meter, voices deeper skepticism. "My opinion is that they're only seeing signals from the surface of the brain," he comments. "I'm concerned that we are extrapolating too far with this technology."