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Hedgehog Pathway a Key Player at Blood-Brain Barrier

Contribution by Elga de Vries en Jack van Horssen to a paper in Science Express

(in cooperation with the research group of Alexandra Prat, Montreal, Canada) that provides compelling evidence suggesting a dual protective role for the Hh pathway at the level of the blood-brain barrier.

The Hedgehog Pathway Promotes Blood-Brain Barrier Integrity and CNS Immune Quiescence

The blood-brain barrier (BBB) is composed of tightly bound endothelial cells (ECs) and perivascular astrocytes that regulate central nervous system (CNS) homeostasis. Here, we show that astrocytes secrete Sonic hedgehog (Shh) and that BBB-ECs express Hh receptors, which together promote BBB formation and integrity during embryonic development and adulthood. Using pharmacological inhibition and genetic inactivation of the Hh signaling pathway in ECs, we also demonstrate a critical role of the Hh pathway in promoting immune quiescence of BBB-ECs by decreasing the expression of proinflammatory mediators and the adhesion and migration of leukocytes, in vivo and in vitro. Overall, the Hh pathway provides a barrier-promoting effect and an endogenous anti-inflammatory balance to CNS-directed immune attacks, as occurs in multiple sclerosis.

Link to the paper: http://www.sciencemag.org/content/early/2011/11/30/science.1206936.full.pdf