The role of free radical generation in increasing cerebrovascular permeability

Free Radic Biol Med. 2011 Sep 1;51(5):967-77. doi: 10.1016/j.freeradbiomed.2011.06.003. Epub 2011 Jun 12.

Abstract

The brain endothelium constitutes a barrier to the passive movement of substances from the blood into the cerebral microenvironment, and disruption of this barrier after a stroke or trauma has potentially fatal consequences. Reactive oxygen species (ROS), which are formed during these cerebrovascular accidents, have a key role in this disruption. ROS are formed constitutively by mitochondria and also by the activation of cell receptors that transduce signals from inflammatory mediators, e.g., activated phospholipase A₂ forms arachidonic acid that interacts with cyclooxygenase and lipoxygenase to generate ROS. Endothelial NADPH oxidase, activated by cytokines, also contributes to ROS. There is a surge in ROS following reperfusion after cerebral ischemia and the interaction of the signaling pathways plays a role in this. This review critically evaluates the literature and concludes that the ischemic penumbra is a consequence of the initial edema resulting from the ROS surge after reperfusion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood-Brain Barrier* / enzymology
  • Blood-Brain Barrier* / pathology
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology
  • Brain Injuries / physiopathology
  • Capillary Permeability
  • Cytokines / metabolism
  • Endothelium / metabolism*
  • Endothelium / pathology
  • Free Radicals / metabolism
  • Humans
  • Inflammation Mediators / metabolism
  • Mitochondria / metabolism*
  • Signal Transduction / physiology
  • Stroke / metabolism*
  • Stroke / pathology
  • Stroke / physiopathology

Substances

  • Cytokines
  • Free Radicals
  • Inflammation Mediators