Arizona Health Sciences

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

TitleHypoxic Stress and Inflammatory Pain Disrupt Blood-Brain Barrier Tight Junctions: Implications for Drug Delivery to the Central Nervous System.
Publication TypeJournal Article
Year of Publication2017
AuthorsLochhead JJ, Ronaldson PT, Davis TP
JournalAAPS J
Volume19
Issue4
Pagination910-920
Date Published2017 Jul
ISSN1550-7416
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.

DOI10.1208/s12248-017-0076-6
Alternate JournalAAPS J
PubMed ID28353217
PubMed Central IDPMC5481481
Grant ListR01 DA011271 / DA / NIDA NIH HHS / United States
R01 NS042652 / NS / NINDS NIH HHS / United States
R01 NS084941 / NS / NINDS NIH HHS / United States
Faculty Member Reference: 
Thomas P Davis, PhD
Jeffrey J. Lochhead, PhD
Patrick T Ronaldson, PhD