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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalAAPS Journal
DOIs
StateAccepted/In press - Mar 28 2017

Fingerprint

Tight Junctions
Blood-Brain Barrier
Central Nervous System
Central Nervous System Diseases
Pain
Pharmaceutical Preparations
Central Nervous System Agents
Permeability
Tight Junction Proteins
Aptitude
Brain
Homeostasis
Inflammation
Therapeutics
Hypoxia

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

@article{cc4f34fbed034dc2970f80015583cfcc,
title = "Hypoxic Stress and Inflammatory Pain Disrupt Blood-Brain Barrier Tight Junctions: Implications for Drug Delivery to the Central Nervous System",
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.",
author = "Lochhead, {Jeffrey J.} and Ronaldson, {Patrick T} and Davis, {Thomas P}",
year = "2017",
month = "3",
day = "28",
doi = "10.1208/s12248-017-0076-6",
language = "English (US)",
pages = "1--11",
journal = "AAPS Journal",
issn = "1550-7416",
publisher = "Springer New York",

}

TY - JOUR

T1 - Hypoxic Stress and Inflammatory Pain Disrupt Blood-Brain Barrier Tight Junctions

T2 - Implications for Drug Delivery to the Central Nervous System

AU - Lochhead, Jeffrey J.

AU - Ronaldson, Patrick T

AU - Davis, Thomas P

PY - 2017/3/28

Y1 - 2017/3/28

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85016125545&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016125545&partnerID=8YFLogxK

U2 - 10.1208/s12248-017-0076-6

DO - 10.1208/s12248-017-0076-6

M3 - Article

C2 - 28353217

AN - SCOPUS:85016125545

SP - 1

EP - 11

JO - AAPS Journal

JF - AAPS Journal

SN - 1550-7416

ER -