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. 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.
Panikashvili
D
D
Department of Pharmacology, Medical Faculty, Hebrew University, Jerusalem 91120, Israel.
Simeonidou
C
C
Ben-Shabat
S
S
Hanus
L
L
Breuer
A
A
Mechoulam
R
R
Shohami
E
E
D000818:Animals; D001095:Arachidonic Acids; D001831:Body Temperature; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D020520:Brain Infarction / Q000517:prevention & control; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002186:Cannabinoids / Q000378:metabolism; D016923:Cell Death; D004195:Disease Models, Animal; D063388:Endocannabinoids; D008401:Gas Chromatography-Mass Spectrometry; D005989:Glycerides / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D016489:Head Injuries, Closed / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D005989:Glycerides; D018696:Neuroprotective Agents; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C094503:glyceryl 2-arachidonate