NADPH Oxidases and Blood-Brain Barrier Dysfunction in Stroke

  • Timo Kahles
  • Sabine Heumüller
  • Ralf P. Brandes
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)


The opening of the blood-brain barrier, brain edema, intracerebral hemorrhage, and loss of neuronal tissue are consequences of ischemic stroke. The phase of ischemia is often followed by reperfusion, either occurring spontaneously or as a result of recanalization therapies such as thrombolysis or mechanical devices. An increased formation of reactive oxygen species (ROS) occurs during ischemia/hypoxia, but most importantly during reperfusion/reoxygenation, and contributes to tissue injury. Although mitochondria have long been considered the primary source of ROS during ischemic stroke and reperfusion, recently NADPH oxidases have been shown to be of great importance for the process, too. All cells in the brain express functional NADPH oxidases, and genetic deletion of p47phox or Nox2 reduces the brain infarct size in mice. The opening of the blood-brain barrier (BBB) within minutes after reperfusion is an early sign of vascular dysfunction after stroke. The initial phase of this process, which involves contraction of endothelial cells, is mediated by NADPH oxidases, and genetic deletion or pharmacological inhibition of the oxidases prevents the BBB opening. In this chapter, the contribution of ROS and the NADPH oxidase in particular for tissue injury and BBB dysfunction in ischemic stroke will be reviewed.


Stroke Reactive oxygen species Ischemia Reperfusion Hypoxia Reoxygenation Brain Endothelium 


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Timo Kahles
    • 1
  • Sabine Heumüller
    • 1
  • Ralf P. Brandes
    • 1
  1. 1.Institut für Kardiovaskuläre Physiologie, Fachbereich Medizin der Goethe-UniversitätFrankfurt am MainGermany

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