Antioxidant properties of the vasoactive endocannabinoid, 2-arachidonoyl glycerol (2-AG).
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.
McCarron
R M
RM
Resuscitative Medicine Department, Naval Medical Research Center, Forest Glen, MD, USA.
Shohami
E
E
Panikashvili
D
D
Chen
Y
Y
Golech
S
S
Strasser
A
A
Mechoulam
R
R
Spatz
M
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects; D001929:Brain Edema / Q000209:etiology*; D002118:Calcium / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D063388:Endocannabinoids; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005989:Glycerides / Q000494:pharmacology*; D016489:Head Injuries, Closed / Q000150:complications* / Q000503:physiopathology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016877:Oxidants / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013113:Spin Labels; D014666:Vasomotor System / Q000187:drug effects*
D000975:Antioxidants; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D003497:Cyclic N-Oxides; D063388:Endocannabinoids; D016166:Free Radical Scavengers; D005989:Glycerides; D016877:Oxidants; D017382:Reactive Oxygen Species; D013113:Spin Labels; C094503:glyceryl 2-arachidonate; D006861:Hydrogen Peroxide; D002118:Calcium; C001803:tempol