Mystery of Blood Brain Barrier Revealed

Until now, scientists have
not known exactly how inflammation weakens the blood-brain barrier (BBB),
allowing toxins and other molecules access to the brain. A new research report
appearing in the June 2014 issue of
The FASEB Journal solves this mystery by showing that a molecule,
called “microRNA-155,” is responsible for cleaving epithelial cells
to create microscopic gaps that let material through. Not only does this
discovery help explain the molecular underpinnings of diseases like multiple
sclerosis, but it also opens an entirely new avenue for developing therapies
that can help penetrate the BBB to deliver lifesaving drugs.

According to Ignacio A,
Romero, PhD, “We are beginning to understand the mechanisms by which the
barrier between the blood and the brain becomes leaky in inflammatory
conditions. Based on these and other findings, drugs that reduce the leakiness
of the barrier have the potential to improve symptoms in many neurological
conditions.” Romero is one of the researchers involved in the work from
the Department of Life, Health and Chemical Sciences of the Biomedical Research
Network at The Open University in the United Kingdom.

To make this discovery,
Romero and colleagues first measured microRNA-155 (miR-155) levels in cultured
human cells and compared them to cells under inflammatory conditions.
Researchers then measured levels in the blood vessels of inflamed brain areas
of patients with MS and compared them to non-inflamed areas. In both cases,
miR-155 was elevated in inflammation. Then, in mice, normal mice were compared
with mice that were genetically altered to lose miR-155.

When an inflammatory
reaction was induced in these two groups of mice, the mice that could not
express miR-155 had a much reduced increase in “leakiness” of the BBB
than normal mice. Finally, scientists investigated in cultured human cells the
mechanism by which miR-155 levels cause leakiness of the barrier and concluded
that miR-155 affects the organization of the complex structures that form the
tight connections between endothelial cells.

“This study has the
potential to be a game-changer in terms of how we treat neurological conditions
and how we deliver drugs to the brain,” said Gerald Weissmann, MD,
editor-in-chief of The
FASEB Journal. “Since it was first discovered, the blood-brain
barrier has always been a touch elusive. Now, after careful analysis, we are
learning exactly how our bodies keep our brains safe, and that microRNA-155 is
a key player.”

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