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Friday Science Review: December 30, 2011

Hedgehog Signaling Upholds Integrity of BBB

University of Montreal ♦ Published in Science, December 23, 2011

The blood-brain barrier (BBB) is a crucial boundary within the body that restricts the migration of blood-borne molecules and immune cells from circulation into the brain. Specialized endothelial cells tightly bound together with junctional proteins ensure that only certain small molecules are able to access the brain. Given that Hedgehog (Hh) signaling has been implicated in multiple sclerosis, a disease characterized by autoimmune destruction of myelin cells, researchers at the University of Montreal hypothesized that Hh signaling may have an influence on the formation of the BBB. They found that astrocytes in close proximity to endothelial cells in the BBB release Hh and that endothelial cells express Hh receptors, in keeping with the theory that Hh signaling is important for the integrity of the BBB. In order to demonstrate that Hh signaling also keeps leukocytes out of contact with the brain, researchers injected mice with cyclopamine, a small molecule inhibitor of the Hh pathway. Indeed, pharmacological inhibition of the Hh pathway led to acute disruption of the BBB and passage of leukocytes into the brain. Together these findings implicate the Hh pathway as being critical in the development and structural integrity of the BBB.

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