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

• Published in: Nature (London) Vol. 413; no. 6855; pp. 527 - 531
• Main Authors: Shohami, Esther, Panikashvili, David, Simeonidou, Constantina, Ben-Shabat, Shimon, Hanuš, Lumír, Breuer, Aviva, Mechoulam, Raphael
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 04.10.2001; Nature Publishing Group
• Subjects: 2-Arachidonoylglycerol; Animals; Arachidonic Acids; Biological and medical sciences; Body Temperature; Brain damage; Brain Edema - etiology; Brain Edema - prevention & control; Brain Infarction - prevention & control; Brain Injuries - drug therapy; Brain Injuries - metabolism; Brain Injuries - pathology; Cannabinoids - metabolism; Cell Death; Disease Models, Animal; Endocannabinoids; Gas Chromatography-Mass Spectrometry; Glycerides - administration & dosage; Glycerides - pharmacology; Glycerides - physiology; Head injuries; Head Injuries, Closed - metabolism; Hippocampus - pathology; Male; Medical sciences; Mice; Neurology; Neuropharmacology; Neuroprotective agent; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacology; Pharmacology. Drug treatments; Receptors, Cannabinoid; Receptors, Drug - metabolism; Rodents; Traumatic brain injury; CB1 cannabinoid receptor; Nervous system diseases; Intravenous administration; Pathophysiology; Arachidonic acid derivatives; Craniocerebral; Rodentia; Diseases of the osteoarticular system; Neuroprotective agent; Cannabinoid; Trauma; Cerebral disorder; Vertebrata; Chemotherapy; Mammalia; Endogenous; Treatment; Mouse; Animal; Central nervous system disease; Skull disease
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35097089

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.