title: Endocannabinoids and neuroprotection.
abstract: Traumatic brain injury (TBI) releases harmful mediators that lead to secondary damage. On the other hand, neuroprotective mediators are also released, and the balance between these classes of mediators determines the final outcome after injury. Recently, it was shown that the endogenous brain cannabinoids anandamide and 2-Arachidonoyl glycerol (2-AG) are also formed after TBI in rat and mouse respectively, and when administered after TBI, they reduce brain damage. In the case of 2-AG, better results are seen when it is administered together with related fatty acid glycerol esters. Significant reduction of brain edema, better clinical recovery, and reduced infarct volume and hippocampal cell death are noted. This new neuroprotective mechanism may involve inhibition of transmitter release and of inflammatory response. 2-AG is also a potent modulator of vascular tone, and counteracts the endothelin (ET-1)-induced vasoconstriction that aggravates brain damage; it may thus help to restore blood supply to the injured brain.
authors.affiliation: Department of Medicinal Chemistry and Natural Products, Hebrew University Medical Faculty, Jerusalem 91120, Israel. mechou@cc.huji.ac.il
authors.forename: R
authors.initials: R
authors.lastname: Mechoulam
authors.forename: M
authors.initials: M
authors.lastname: Spatz
authors.forename: E
authors.initials: E
authors.lastname: Shohami
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D001925:Brain Damage, Chronic / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000378:metabolism / Q000627:therapeutic use*; D063388:Endocannabinoids; D006801:Humans; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D018696:Neuroprotective Agents