An endogenous cannabinoid (2-AG) is neuroprotective after brain injury

Traumatic brain injury triggers the accumulation of harmful mediators that may lead to secondary damage(1,2). Protective mechanisms to attenuate damag e are also set in motion(2). 2-Arachidonoyl glycerol (2-AG) is an endogenou s cannabinoid, identified both in the periphery(3) and in the brain(4), but its physiological roles have been only partially clarified(5-7). Here we s how that, after injury to the mouse brain, 2-AG may have a neuroprotective role in which the cannabinoid system is involved. After closed head injury (CHI) in mice, the level of endogenous 2-AG was significantly elevated. We administered synthetic 2-AG to mice after CHI and found significant reducti on of brain oedema, better clinical recovery, reduced infarct volume and re duced hippocampal cell death compared with controls. When 2-AG was administ ered together with additional inactive 2-acyl-glycerols that are normally p resent in the brain, functional recovery was significantly enhanced. The be neficial effect of 2-AG was dose-dependently attenuated by SR-141761A, an a ntagonist of the CB1 cannabinoid receptor.