tailieunhanh - Báo cáo khoa học: Post-ischemic brain damage: the endocannabinoid system in the mechanisms of neuronal death

An emerging body of evidence supports a key role for the endocannabinoid system in numerous physiological and pathological mechanisms of the cen-tral nervous system. In the recent past, many experimental studies have examined the putative protective or toxic effects of drugs interacting with cannabinoid receptors or have measured the brain levels of endocannabi-noids inin vitro and in vivo models of cerebral ischemia. | MINIREVIEW Post-ischemic brain damage the endocannabinoid system in the mechanisms of neuronal death Domenico E. Pellegrini-Giampietro1 Guido Mannaioni1 and Giacinto Bagetta2 1 Department of Preclinicaland ClinicalPharmacology University of Florence Italy 2 Department of Pharmacobiology and University Center for Adaptive Disorders and Headache UCADH University of Calabria Arcavacata di Rende CS Italy Keywords ananadamide 2-arachidonoylglycerol cannabinoids CB receptors cerebral ischemia endocannabinoids neuroprotection neurotoxicity oxygen-glucose deprivation stroke Correspondence D. E. Pellegrini-Giampietro Department of Pharmacology University of Florence Viale Pieraccini 6 50139 Firenze Italy Fax 30 055 4271 280 Tel 39 055 4271 205 E-mail Received 27 June 2008 revised 30 September 2008 accepted 24 October 2008 doi An emerging body of evidence supports a key role for the endocannabinoid system in numerous physiological and pathological mechanisms of the central nervous system. In the recent past many experimental studies have examined the putative protective or toxic effects of drugs interacting with cannabinoid receptors or have measured the brain levels of endocannabinoids in in vitro and in vivo models of cerebral ischemia. The results of these studies have been rather conflicting in supporting either a beneficial or a detrimental role for the endocannabinoid system in post-ischemic neuronal death in that cannabinoid receptor agonists and antagonists have both been demonstrated to produce either protective or toxic responses in ischemia depending on a number of factors. Among these the dose of the administered drug and the specific endocannabinoid that accumulates in each particular model appear to be of particular importance. Other mechanisms that have been put forward to explain these discrepant results are the effects of cannabinoid receptor activation on the modulation of excitatory and .