By tethering the water channel protein, Aquaporin-4 (AQP4), to the tips of brain cells, Syntrophin keeps the openings for water right next to blood vessels. Without Syntrophin, the water channels are everywhere on the brain cells except where they are supposed to be, the scientists found.
"The brain is in a very unique environment," says Peter Agre, M.D., a professor in the department of biological chemistry, part of the Johns Hopkins School of Medicine's Institute for Basic Biomedical Sciences, and an author of the report. "If you sprain your ankle, it has room to swell. If you hurt your brain, swelling can kill. The skull provides protection, but its rigidity can be a potentially lethal hazard as well."
In addition to impacting research into brain swelling, the finding also creates a new vision of the invisible barrier between the blood and the brain, one that involves a separate barrier for water, the scientists suggest.
"We think the interaction of the water channel and its tether helps regulate water flow in the brain," says lead author John Neely, Ph.D., a second-year medical student at Hopkins. "Together, AQP4 and Syntrophin appear to represent a vital control point for water in the blood-brain barrier."
Normally located in specialized brain cells called astrocytes, the water channel is clearly involved with starting down the slippery slope toward brain swelling, says Agre. Astrocytes, which make up about 50 percent of the brain's tissue, act as a bridge between blood vessels and impulse-sending neurons.
Usually pressed up to the blood vessel wall, the tips of astrocytes take on water and swell within minutes of a brain injury. AQP
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
4-Feb-2002