title: Endocannabinoids and traumatic brain injury.
abstract: Traumatic brain injury (TBI) represents the leading cause of death in young individuals. It triggers the accumulation of harmful mediators, leading to secondary damage, yet protective mechanisms are also set in motion. The endocannabinoid (eCB) system consists of ligands, such as anandamide and 2-arachidonoyl-glycerol (2-AG), receptors (e.g. CB1, CB2), transporters and enzymes, which are responsible for the 'on-demand' synthesis and degradation of these lipid mediators. There is a large body of evidence showing that eCB are markedly increased in response to pathogenic events. This fact, as well as numerous studies on experimental models of brain toxicity, neuroinflammation and trauma supports the notion that the eCB are part of the brain's compensatory or repair mechanisms. These are mediated via CB receptors signalling pathways that are linked to neuronal survival and repair. The levels of 2-AG, the most highly abundant eCB, are significantly elevated after TBI and when administered to TBI mice, 2-AG decreases brain oedema, inflammation and infarct volume and improves clinical recovery. The role of CB1 in mediating these effects was demonstrated using selective antagonists or CB1 knockout mice. CB2 were shown in other models of brain insults to reduce white blood cell rolling and adhesion, to reduce infarct size and to improve motor function. This review is focused on the role the eCB system plays as a self-neuroprotective mechanism and its potential as a basis for the development of novel therapeutic modality for the treatment of CNS pathologies with special emphasis on TBI.
authors.affiliation: The Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Israel. esty@cc.huji.ac.il
authors.forename: Esther
authors.initials: E
authors.lastname: Shohami
authors.forename: Ayelet
authors.initials: A
authors.lastname: Cohen-Yeshurun
authors.forename: Lital
authors.initials: L
authors.lastname: Magid
authors.forename: Merav
authors.initials: M
authors.lastname: Algali
authors.forename: Raphael
authors.initials: R
authors.lastname: Mechoulam
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D063388:Endocannabinoids; D006801:Humans; D043882:Receptors, Cannabinoid / Q000378:metabolism*
chemical_list: D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D043882:Receptors, Cannabinoid