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Objectives : Sesamin, a major lignan in sesame seeds, has been reported to have neuroprotective effects against in vitro ischemia and in vivo MCAo-reperfusion cerebral ischemia model, however, there is no reports in an in vivo global cerebral ischemia model. The purpose of the study was to investigate the neuroprotective effect of sesamin in global cerebral ischemia induced by four-vessel occl usion (4-VO) in rats through inhibition of microglial activation in this model.Methods : The neuroprotective effects were investigated using a 10 min of 4-VO ischemia rat model by measuring intact pyramidal neurons in the CA1 region of the hip pocampus using Nissle staining. The antiinflammatory or reducing neurotoxicity effect was investiga ted using immunohistochemisty, RT-PCR and western blot analysis of inflammatory or neurotoxic mediators.Results : Intraperitoneal injection of sesamin at doses of 0.3, 1.0, 3.0 , and 10.0 mg/kg at 0 min and 90 min after ischemia conferred 26.6%, 30.1%, 42.5%, and 30.5% neuropr otection, respectively, compared to the vehicle-treated control group. A 3.0 mg/kg dose of sesamin inhibited microglia activation and consequently, cyclooxygenase-2, inducible nitric oxide, and interleukine-1β e xpressions at 48 h after reperfusion.Conclusions : Sesamin protects neuronal cell death through inhibition of mic roglial activation or the production of neurotoxic metabolites and proinflammatory mediators by micr oglia such as COX-2, iNOS and IL-1β in global cerebral ischemia.Key words : Sesamin, Global cerebral ischemia, 4-vessel occlusion, Microgl ial activation, Neuroprotection

Sesamin attenuates neuronal damage through inhibition of microglial activation following global cerebral ischemia in rats