Arizona Health Sciences

Targeting transporters: promoting blood-brain barrier repair in response to oxidative stress injury.

TitleTargeting transporters: promoting blood-brain barrier repair in response to oxidative stress injury.
Publication TypeJournal Article
Year of Publication2015
AuthorsRonaldson PT, Davis TP
JournalBrain Res
Volume1623
Pagination39-52
Date Published2015 Oct 14
ISSN1872-6240
KeywordsAnimals, Blood-Brain Barrier, Humans, Oxidative Stress
Abstract

The blood-brain barrier (BBB) is a physical and biochemical barrier that precisely regulates the ability of endogenous and exogenous substances to accumulate within brain tissue. It possesses structural and biochemical features (i.e., tight junction and adherens junction protein complexes, influx and efflux transporters) that work in concert to control solute permeation. Oxidative stress, a critical component of several diseases including cerebral hypoxia/ischemia and peripheral inflammatory pain, can cause considerable injury to the BBB and lead to significant CNS pathology. This suggests a critical need for novel therapeutic approaches that can protect the BBB in diseases with an oxidative stress component. Recent studies have identified molecular targets (i.e., putative membrane transporters, intracellular signaling systems) that can be exploited for optimization of endothelial drug delivery or for control of transport of endogenous substrates such as the antioxidant glutathione (GSH). In particular, targeting transporters offers a unique approach to protect BBB integrity by promoting repair of cell-cell interactions at the level of the brain microvascular endothelium. This review summarizes current knowledge in this area and emphasizes those targets that present considerable opportunity for providing BBB protection and/or promoting BBB repair in the setting of oxidative stress. This article is part of a Special Issue entitled SI: Cell Interactions In Stroke.

DOI10.1016/j.brainres.2015.03.018
Alternate JournalBrain Res.
PubMed ID25796436
PubMed Central IDPMC4569519
Grant ListR01 DA11271 / DA / NIDA NIH HHS / United States
R01 NS039592 / NS / NINDS NIH HHS / United States
R01 NS084941 / NS / NINDS NIH HHS / United States
R01 NS042652 / NS / NINDS NIH HHS / United States
R01 NS42652 / NS / NINDS NIH HHS / United States
R01 DA011271 / DA / NIDA NIH HHS / United States
Faculty Member Reference: 
Thomas P Davis, PhD
Patrick T Ronaldson, PhD