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UCSD researchers decipher function of blood-brain barrier in bacterial meningitis

The first line of defense used by the human blood-brain barrier in response to bacterial meningitis is described by researchers at the University of California, San Diego (UCSD) School of Medicine in a study published in the September 2, 2003 issue of The Journal of Clinical Investigation. The scientists also describe two bacterial factors specific to the meningitis pathogen that thwart the normal protective role of the blood-brain barrier, leading to serious infection.

Composed of a layer of blood vessels called brain microvascular endothelial cells (BMEC), the blood-brain barrier separates the brain and its surrounding tissues from the circulating blood, tightly regulating the flow of nutrients and molecules and thereby maintaining the proper biochemical conditions for normal brain function.

Bacterial meningitis, a serious brain infection, can develop rapidly into a life-threatening infection even in previously healthy children or adults. Bacteria-producing meningitis enter the human bloodstream, are carried toward the brain, and somehow manage to cross the defensive line of the blood-brain barrier.

Using an experimental blood-brain barrier established by growing layers of human BMEC in tissue culture plates, the UCSD team observed that a specific set of 80 genes in the blood-brain barrier were activated when exposed to the pathogen Group B Streptococcus (GBS), the leading cause of bacterial meningitis in human newborn infants. These genes released proteins that mobilized human white blood cells called neutrophils, which are attracted to sites of infection.

Lead author Kelly Doran, Ph.D., assistant adjunct professor of pediatrics in the UCSD Division of Infectious Diseases, said "these findings demonstrate a novel function of the blood-brain barrier, to act as a sentry that detects the threat of a bacterial pathogen and responds by triggering an immune response to clear the infection."

According to senior author V
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Contact: Sue Pondrom
spondrom@ucsd.edu
619-543-6163
University of California - San Diego
2-Sep-2003


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