Antioxidant properties of the vasoactive endocannabinoid, 2-arachidonoyl glycerol (2-AG)

Acta Neurochir Suppl. 2003;86:271-5. doi: 10.1007/978-3-7091-0651-8_59.

Abstract

Reactive oxygen species (ROS) were shown to play a role in altering blood-brain barrier (BBB) permeability and formation of brain edema induced by trauma and/or ischemia. 2-arachidonoyl glycerol (2-AG), a novel, potent vasodilatory and cytoprotective endocannabinoid has been implicated to act as an antioxidative agent. This study examines: 1) the possible 2-AG modulation of BBB injury and edema formation induced by closed head injury (CHI); and 2) comparable effects between 2-AG and 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TPL), a known antioxidant nitroxide on endothelial Ca2+ and cytoskeletal responses to H2O2 (ROS). 2-AG treatment reduced the CHI-induced increase in BBB permeability and brain edema. The endothelial H2O2-stimulated Ca2+ mobilization and cytoskeleton (vimentin) rearrangement was modified by either 2-AG or TPL. These findings provide evidence of 2-AG antioxidant activity and are consistent with the involvement of ROS in the pathomechanism of CHI-induced BBB injury and brain edema.

Publication types

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

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Arachidonic Acids / pharmacology*
  • Blood-Brain Barrier* / drug effects
  • Brain Edema / etiology*
  • Calcium / metabolism
  • Cannabinoid Receptor Modulators / pharmacology*
  • Capillary Permeability / drug effects
  • Cyclic N-Oxides / pharmacology
  • Cytoskeleton / drug effects
  • Endocannabinoids*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Free Radical Scavengers / pharmacology
  • Glycerides / pharmacology*
  • Head Injuries, Closed / complications*
  • Head Injuries, Closed / physiopathology*
  • Hydrogen Peroxide / pharmacology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Oxidants / pharmacology
  • Reactive Oxygen Species / metabolism
  • Spin Labels
  • Vasomotor System / drug effects*

Substances

  • Antioxidants
  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Cyclic N-Oxides
  • Endocannabinoids
  • Free Radical Scavengers
  • Glycerides
  • Oxidants
  • Reactive Oxygen Species
  • Spin Labels
  • glyceryl 2-arachidonate
  • Hydrogen Peroxide
  • Calcium
  • tempol