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How Invaders Break Through the Brain's Great Wall

Some bacteria pierce the imposing blood-brain barrier by breaking links in the chain; sneakier ones do it by fooling the guard cells.

By Megan Talkington
Oct 15, 2009 5:00 AMNov 12, 2019 4:21 AM


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One of biology’s great mysteries is the blood-brain barrier, which lines blood vessels in the brain. It normally keeps the brain healthy by preventing bacteria and large molecules in the bloodstream from reaching the central nervous system. A few fearsome agents, however—including meningitis pathogens and cancer cells—somehow make it across. Several research teams have recently announced fresh insights on how the invaders get through, findings that also suggest new ways to send drugs across the barrier to go after them.

Researchers in the U.S. and the U.K. investigated how three major meningitis-producing bacteria avoid being blocked by barrier cells in the brain. They discovered that all three lock onto a barrier-cell protein called the laminin receptor. From there the germs are sent on to another receptor and into the brain, where infection-fighting immune cells cannot reach them. In an effort to provide broad protection against meningitis, the researchers are now developing a vaccine that would prevent the bacteria from recognizing the laminin receptor, according to Elaine Tuomanen, a leader of the study and a physician at St. Jude Children’s Research Hospital in Memphis, Tennessee.

A separate study, led by microbiologist Xavier Nassif at the French National Institute for Health and Medical Research, uncovered another trick that bacteria use to enter the brain: Instead of passing through barrier cells, Neisseria meningitidis (one of the three meningitis bacteria) opens up gaps between them by disabling the proteins that lock the cells together. The finding raises the possibility that drugs could be delivered by this same route to treat brain infections or diseases such as Alzheimer’s or cancer.

Other teams are making promising advances in drug delivery to the brain. Researchers at the Institute of Bioengineering and Nanotechnology in Singapore constructed drugs in the form of peptide nanoparticles that can ford the blood-brain barrier in rabbits and kill both bacteria and fungi.

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