BACKGROUND: Endoplasmic reticulum (ER) stress impairs ER functions and leads to the accumulation of unfolded or misfolded proteins in the ER lumen. ER stress-induced cell death plays an important role in cerebral ischemia. Edaravon (3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent and novel scavenger of free radicals that inhibit delayed neuronal death, as demonstrated by in vitro and animal studies. However, its effect on ER stress and induced neuronal apoptosis in a rat model of brief middle cerebral artery occlusion remains unclear. OBJECTIVE: To explore the effects of edaravone on the expression of ER stress-related factors and neuronal apoptosis, based on the hypothesis that edaravone influences ER stress in a rat model of cerebral ischemia/reperfusion. DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Laboratory of Department of Neurology, Xiangya Hospital and the Department of Laboratory Animals, Xiangya Medical College, Central South University in China from June 2005 to May 2006. MATERIALS: Edaravone was purchased from Simcere Pharmaceutical Group, China. METHODS: A total of 216 adult, male, Sprague Dawley rats were randomly assigned to sham-surgery, model and edaravone groups, with 72 rats in each group. Brief middle cerebral artery occlusion was established in the model and edaravone groups. In addition, the edaravone group rats were injected with 3 mg/kg edaravone through the tail vein. MAIN OUTCOME MEASURES: RNA-dependent protein kinase-like endoplasmic reticulum eukaryotic translation initiation factor 2α kinase (PERK) and C/EBP homology protein (CHOP) mRNA expression in the ischemic parietal cortex was determined by reverse transcription- polymerase chain reaction; phosphorylated PERK and CHOP protein expression was detected by immunohistochemistry; neuronal apoptosis was detected by TdT-mediated-dUTP nick end labeling. RESULTS: Neurological deficit scores were significantly reduced in the edaravone group compared to the model group at 12, 24, and 72 hours following reperfusion (P < 0.05). In addition, PERK and CHOP mRNA as well as phosphorylated PERK and CHOP protein expression were significantly reduced in the edaravone group compared to the model group at 1, 3, and 6 hours following reperfusion (P < 0.05, P < 0.01). CHOP mRNA expression was decreased in the edaravone group compared to the model group at 3, 6, 12, and 24 hours following reperfusion (P < 0.01), while CHOP protein expression was less than the model group at 6, 12, and 24 hours following reperfusion (P < 0.05). CONCLUSION: Edaravone treatment resulted in decreased PERK and CHOP expression following ischemia/reperfusion, as well as reduced neuronal apoptosis. Edaravone exhibited a neuroprotective role by inhibiting endoplasmic reticulum stress. BACKGROUND: Endoplasmic reticulum (ER) stress impairs ER functions and leads to the accumulation of unfolded or misfolded proteins in the ER lumen. ER stress-induced cell death plays an important role in cerebral ischemia. Edaravon (3-methyl-1-phenyl- 2-pyrazolin-5-one) is a potent and novel scavenger of free radicals that inhibit delayed neuronal death, as demonstrated by in vitro and animal studies. However, its effect on ER stress and induced neuronal apoptosis in a rat model of brief middle OBJECTIVE: To explore the effects of edaravone on the expression of ER stress-related factors and neuronal apoptosis, based on the hypothesis that edaravone influences ER stress in a rat model of cerebral ischemia / reperfusion. DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Laboratory of Department of Neurology, Xiangya Hospital and the Department of Laboratory Animals, Xiangya Medical College, Central South Universi METHODS: A total of 216 adult, male, Sprague Dawley rats were randomly assigned to sham-surgery, model and edaravone groups, with 72 Brief middle cerebral artery occlusion was established in the model and edaravone groups. In addition, the edaravone group rats were injected with 3 mg / kg edaravone through the tail vein. MAIN OUTCOME MEASURES: RNA-dependent protein kinase-like endoplasmic reticulum eukaryotic translation initiation factor 2α kinase (PERK) and C / EBP homology protein (CHOP) mRNA expression in the ischemic parietal cortex was determined by reverse transcription- polymerase chain reaction; phosphorylated PERK and CHOP protein expression was detected by immunohistochemistry; neuronal apoptosis was detected by TdT-mediated-dUTP nick end labeling. RESULTS: Neurological deficit scores were significantly reduced in the edaravone group compared tThe model group at 12, 24, and 72 hours following reperfusion (P <0.05). In addition, PERK and CHOP mRNA expressions were significantly reduced in the edaravone group compared to the model group at 1 (P <0.05, P <0.01). CHOP mRNA expression was decreased in the edaravone group compared to the model group at 3, 6, 12, and 24 hours following reperfusion (P <0.01) while CHOP protein expression was less than the model group at 6, 12, and 24 hours following reperfusion (P <0.05). CONCLUSION: Edaravone treatment resulted in decreased PERK and CHOP expression following ischemia / reperfusion, as well as reduced neuronal apoptosis. had a neuroprotective role by inhibiting endoplasmic reticulum stress.