TY - JOUR
T1 - An endogenous cannabinoid (2-AG) is neuroprotective after brain injury
AU - Panikashvili, David
AU - Simeonidou, Constantina
AU - Ben-Shabat, Shimon
AU - Hanuš, Lumír
AU - Breuer, Aviva
AU - Mechoulam, Raphael
AU - Shohami, Esther
PY - 2001/10/4
Y1 - 2001/10/4
N2 - Traumatic brain injury triggers the accumulation of harmful mediators that may lead to secondary damage. Protective mechanisms to attenuate damage are also set in motion. 2-Arachidonoyl glycerol (2-AG) is an endogenous cannabinoid, identified both in the periphery and in the brain, but its physiological roles have been only partially clarified. Here we show 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 reduction of brain oedema, better clinical recovery, reduced infarct volume and reduced hippocampal cell death compared with controls. When 2-AG was administered together with additional inactive 2-acyl-glycerols that are normally present in the brain, functional recovery was significantly enhanced. The beneficial effect of 2-AG was dose-dependently attenuated by SR-141761A, an antagonist of the CB1 cannabinoid receptor.
AB - Traumatic brain injury triggers the accumulation of harmful mediators that may lead to secondary damage. Protective mechanisms to attenuate damage are also set in motion. 2-Arachidonoyl glycerol (2-AG) is an endogenous cannabinoid, identified both in the periphery and in the brain, but its physiological roles have been only partially clarified. Here we show 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 reduction of brain oedema, better clinical recovery, reduced infarct volume and reduced hippocampal cell death compared with controls. When 2-AG was administered together with additional inactive 2-acyl-glycerols that are normally present in the brain, functional recovery was significantly enhanced. The beneficial effect of 2-AG was dose-dependently attenuated by SR-141761A, an antagonist of the CB1 cannabinoid receptor.
UR - http://www.scopus.com/inward/record.url?scp=0035807380&partnerID=8YFLogxK
U2 - 10.1038/35097089
DO - 10.1038/35097089
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C2 - 11586361
AN - SCOPUS:0035807380
SN - 0028-0836
VL - 413
SP - 527
EP - 531
JO - Nature
JF - Nature
IS - 6855
ER -