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The AAPS Journal

, Volume 19, Issue 4, pp 910–920 | Cite as

Hypoxic Stress and Inflammatory Pain Disrupt Blood-Brain Barrier Tight Junctions: Implications for Drug Delivery to the Central Nervous System

  • Jeffrey J. Lochhead
  • Patrick T. Ronaldson
  • Thomas P. Davis
Review Article Theme: CNS Barriers in Health and Disease
Part of the following topical collections:
  1. Theme: CNS Barriers in Health and Disease

Abstract

A functional blood-brain barrier (BBB) is necessary to maintain central nervous system (CNS) homeostasis. Many diseases affecting the CNS, however, alter the functional integrity of the BBB. It has been shown that various diseases and physiological stressors can impact the BBB’s ability to selectively restrict passage of substances from the blood to the brain. Modifications of the BBB’s permeability properties can potentially contribute to the pathophysiology of CNS diseases and result in altered brain delivery of therapeutic agents. Hypoxia and/or inflammation are central components of a number of diseases affecting the CNS. A number of studies indicate hypoxia or inflammatory pain increase BBB paracellular permeability, induce changes in the expression and/or localization of tight junction proteins, and affect CNS drug uptake. In this review, we look at what is currently known with regard to BBB disruption following a hypoxic or inflammatory insult in vivo. Potential mechanisms involved in altering tight junction components at the BBB are also discussed. A more detailed understanding of the mediators involved in changing BBB functional integrity in response to hypoxia or inflammatory pain could potentially lead to new treatments for CNS diseases with hypoxic or inflammatory components. Additionally, greater insight into the mechanisms involved in TJ rearrangement at the BBB may lead to novel strategies to pharmacologically increase delivery of drugs to the CNS.

KEY WORDS

blood-brain barrier drug delivery hypoxia pain tight junctions 

Notes

Acknowledgements

This work was supported by NIH grants 5 RO1 NS 42652 and 5 RO1 DA 11271 awarded to TPD.

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Copyright information

© American Association of Pharmaceutical Scientists 2017

Authors and Affiliations

  • Jeffrey J. Lochhead
    • 1
  • Patrick T. Ronaldson
    • 1
  • Thomas P. Davis
    • 1
  1. 1.Department of PharmacologyUniversity of ArizonaTucsonUSA

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