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.