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Cell-specific blood-brain barrier regulation in health and disease: a focus on hypoxia


Engelhardt, S; Patkar, S; Ogunshola, O O (2014). Cell-specific blood-brain barrier regulation in health and disease: a focus on hypoxia. British Journal of Pharmacology, 171(5):1210-1230.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Physiology
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2014
Deposited On:23 Oct 2014 09:05
Last Modified:05 Apr 2016 18:25
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0007-1188
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1111/bph.12489
PubMed ID:24641185

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