UM RESEARCHERS DISCOVER "KEY" TO BLOOD-BRAIN BARRIER

Researchers at the University of Maryland School of Medicine in Baltimore have identified a receptor in the human brain that regulates the interface between the bloodstream and the brain, which is known as the blood-brain barrier. This breakthrough could lead to a better understanding of this nearly impenetrable barrier and to treatment of diseases that affect the brain, such as Multiple Sclerosis, brain tumors, meningitis, Alzheimer's disease, and HIV infection. The findings are published in the January issue of the Journal of Neurochemistry.

The blood-brain barrier is a collection of cells that press together to block many substances from entering the brain, while allowing others to pass. For years, scientists knew little about how this barrier was regulated or why certain diseases are able to manipulate the barrier and infect the brain.

Earlier research conducted at the University of Maryland School of Medicine found that two proteins, known as zonulin and zot, unlock the cell barrier in the intestine. The proteins attach themselves to receptors in the intestine to open the junctions between the cells and allow substances to be absorbed. The new research indicates that zonulin and zot also react with similar receptors in the brain.

"The blood-brain barrier is like a gateway to the brain. It is almost always locked, keeping out many diseases. Unfortunately, it also keeps out medications as well. Almost nothing can pass," explains lead author Alessio Fasano, M.D., professor of pediatrics and physiology at the University of Maryland School of Medicine, and director of Pediatric Gastroenterology at the University of Maryland Hospital for Children. "First we discovered the key, and now we've found the lock that fits that key to open the gateway into the brain. This discovery could help us open that gateway," explains Dr. Fasano.

Dr. Fasano and his team studied brain tissue samples obtained from a brain and tissue bank at the University of Maryland. The brain tissue was treated with purified zonulin and zot proteins, then examined under a microscope. Researchers observed the zonulin and zot proteins binding with the brain tissue. Next, they compared the results to tests on tissue samples from the intestines.

"We've known about the blood-brain barrier for more than 100 years, but we've never been able to figure out how it worked. Now we have a new piece to the puzzle," says Dr. Fasano.

"The identification of these proteins in the human brain holds the promise of allowing us to deliver new types of medications across the blood-brain barrier. It would be a boon to humanity if the blood-brain barrier could be opened briefly, and safely, to allow passage of a new generation of drugs into the brain," says Ronald Zielke, Ph.D. co- author, professor of pediatrics and director of the brain and tissue bank at the University of Maryland School of Medicine.

Dr. Fasano adds that more research is needed to understand how zonulin and zot work during the formation and development of the brain. The current study was funded by a grant from the National Institutes of Health.