title: Cell-specific blood-brain barrier regulation in health and disease: a focus on hypoxia.
abstract: The blood-brain barrier (BBB) is a complex vascular structure consisting of microvascular endothelial cells that line the vessel wall, astrocyte end-feet, pericytes, as well as the basal lamina. BBB cells act in concert to maintain the characteristic impermeable and low paracellular flux of the brain vascular network, thus ensuring a homeostatic neuronal environment. Alterations in BBB stability that occur during injury have dire consequences on disease progression and it is clear that BBB cell-specific responses, positive or negative, must make a significant contribution to injury outcome. Reduced oxygenation, or hypoxia, is a characteristic of many brain diseases that significantly increases barrier permeability. Recent data suggest that hypoxia-inducible factor (HIF-1), the master regulator of the hypoxic response, probably mediates many hypoxic effects either directly or indirectly via its target genes. This review discusses current knowledge of physiological cell-specific regulation of barrier function, their responses to hypoxia as well as consequences of hypoxic- and HIF-1-mediated mechanisms on barrier integrity during select brain diseases. In the final sections, the potential of current advances in targeting HIF-1 as a therapeutic strategy will be overviewed.
authors.affiliation: Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Engelhardt
authors.forename: S
authors.initials: S
authors.lastname: Patkar
authors.forename: O O
authors.initials: OO
authors.lastname: Ogunshola
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D020286:Pericytes / Q000378:metabolism
chemical_list: D051793:Hypoxia-Inducible Factor 1
keywords: BBB cell-specific response; HIF-1; astrocytes; endothelial cells; hypoxia; neurodegenerative diseases; pericytes