Oxidative stress increases blood-brain barrier permeability and induces alterations in occludin during hypoxia-reoxygenation

Jeffrey J. Lochhead, Gwen McCaffrey, Colleen E. Quigley, Jessica Finch, Kristin M. Demarco, Nicole Nametz, Thomas P Davis

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

The blood-brain barrier (BBB) has a critical role in central nervous system homeostasis. Intercellular tight junction (TJ) protein complexes of the brain microvasculature limit paracellular diffusion of substances from the blood into the brain. Hypoxia and reoxygenation (HR) is a central component to numerous disease states and pathologic conditions. We have previously shown that HR can influence the permeability of the BBB as well as the critical TJ protein occludin. During HR, free radicals are produced, which may lead to oxidative stress. Using the free radical scavenger tempol (200 mg/kg, intraperitoneal), we show that oxidative stress produced during HR (6% O 2 for 1 h, followed by room air for 20 min) mediates an increase in BBB permeability in vivo using in situ brain perfusion. We also show that these changes are associated with alterations in the structure and localization of occludin. Our data indicate that oxidative stress is associated with movement of occludin away from the TJ. Furthermore, subcellular fractionation of cerebral microvessels reveals alterations in occludin oligomeric assemblies in TJ associated with plasma membrane lipid rafts. Our data suggest that pharmacological inhibition of disease states with an HR component may help preserve BBB functional integrity.

Original languageEnglish (US)
Pages (from-to)1625-1636
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume30
Issue number9
DOIs
StatePublished - 2010

Fingerprint

Occludin
Blood-Brain Barrier
Permeability
Oxidative Stress
Tight Junction Proteins
Tight Junctions
Microvessels
Brain
Free Radical Scavengers
Intercellular Junctions
Membrane Lipids
Free Radicals
Homeostasis
Central Nervous System
Perfusion
Air
Cell Membrane
Hypoxia
Pharmacology

Keywords

  • animal models
  • antioxidants
  • bloodbrain barrier
  • confocal microscopy
  • free radicals

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology
  • Medicine(all)

Cite this

Oxidative stress increases blood-brain barrier permeability and induces alterations in occludin during hypoxia-reoxygenation. / Lochhead, Jeffrey J.; McCaffrey, Gwen; Quigley, Colleen E.; Finch, Jessica; Demarco, Kristin M.; Nametz, Nicole; Davis, Thomas P.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 30, No. 9, 2010, p. 1625-1636.

Research output: Contribution to journalArticle

Lochhead, Jeffrey J. ; McCaffrey, Gwen ; Quigley, Colleen E. ; Finch, Jessica ; Demarco, Kristin M. ; Nametz, Nicole ; Davis, Thomas P. / Oxidative stress increases blood-brain barrier permeability and induces alterations in occludin during hypoxia-reoxygenation. In: Journal of Cerebral Blood Flow and Metabolism. 2010 ; Vol. 30, No. 9. pp. 1625-1636.
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