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HIF-1 at the blood-brain barrier: a mediator of permeability?


Ogunshola, Omolara O; Al-Ahmad, Abraham (2012). HIF-1 at the blood-brain barrier: a mediator of permeability? High Altitude Medicine & Biology, 13(3):153-161.

Abstract

The importance of the blood-brain barrier (BBB) in maintaining brain homeostasis cannot be better appreciated than during disease states, where disruption of its function is associated with dramatic detrimental clinical outcome. For decades, neuroscientists and neurobiologists investigated most neurological diseases under the prism of a neuro-centric view, considering the contribution of non-neural components of the CNS (BBB, choroid plexus) negligible or even irrelevant. However, recent reviews have highlighted the importance of BBB breakdown in major neurological diseases. Hypoxia, as well as hypoxia/reoxygenation, are key components of many neurological diseases and have been shown to contribute to barrier disturbance and dysfunction significantly. Since the master regulator of the hypoxic response, hypoxia inducible factor 1 (HIF-1), is a key determinant for adaptation of cells and tissues to oxygen deprivation, it is likely that this transcription factor also plays a key role in barrier permeability. The possible future use of HIF-1 stabilizers for treatment of diseases characterized by oxygen deprivation to increase neuronal/cell survival means this question is now very pertinent. This review will focus its attention on the role of HIF-1 in BBB breakdown following hypoxic/ischemic injury and the implications for such therapies in a clinical setting.

Abstract

The importance of the blood-brain barrier (BBB) in maintaining brain homeostasis cannot be better appreciated than during disease states, where disruption of its function is associated with dramatic detrimental clinical outcome. For decades, neuroscientists and neurobiologists investigated most neurological diseases under the prism of a neuro-centric view, considering the contribution of non-neural components of the CNS (BBB, choroid plexus) negligible or even irrelevant. However, recent reviews have highlighted the importance of BBB breakdown in major neurological diseases. Hypoxia, as well as hypoxia/reoxygenation, are key components of many neurological diseases and have been shown to contribute to barrier disturbance and dysfunction significantly. Since the master regulator of the hypoxic response, hypoxia inducible factor 1 (HIF-1), is a key determinant for adaptation of cells and tissues to oxygen deprivation, it is likely that this transcription factor also plays a key role in barrier permeability. The possible future use of HIF-1 stabilizers for treatment of diseases characterized by oxygen deprivation to increase neuronal/cell survival means this question is now very pertinent. This review will focus its attention on the role of HIF-1 in BBB breakdown following hypoxic/ischemic injury and the implications for such therapies in a clinical setting.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
05 Vetsuisse Faculty > Institute of Veterinary Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2012
Deposited On:14 Feb 2013 14:14
Last Modified:05 Apr 2016 16:31
Publisher:Mary Ann Liebert
ISSN:1527-0297
Additional Information:This is a copy of an article published in the High Altitude Medicine & Biology ©2012 [copyright Mary Ann Liebert, Inc.]; High Altitude Medicine & Biology is available online at: http://www.liebertonline.com.
Publisher DOI:https://doi.org/10.1089/ham.2012.1052
PubMed ID:22994514

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