Influence of edaravone on Notch1 and nuclear factor-kappaB in rats with cerebral ischemia/reperfusion injury

Yonglong Wang; Zhiyou Cai; Yong Luo; Jiaming Gong

摘要：BACKGROUND: It has been demonstrated that edaravone has a a neuroprotective role, inhibits free radical increase, and reduces cell apoptosis. The Notch pathway is a key factor in neurogenesis and cellular apoptosis.The proinflammatory transcription factor nuclear factor-kappaB (NF-κB) plays an important role in inflammation and oxidation.OBJECTIVE: To observe the influence of edaravone on Notch1 and NF-κB mRNA and protein expression in rats with focal cerebral ischemia/reperfusion injury.DESIGN, TIME AND SETTING: This randomized controlled neural and molecular biology experiment was performed at the Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, and the Chongqing Key Laboratory of Neurology between July 2007 and May 2008.MATERIALS: Thirty female Wistar rats were used. Edaravone was purchased from Jiangsu Xiansheng Pharmaceutical Limited Company, China.METHODS: Wistar rats were randomly divided into five groups (n = 6). Thread was inserted into the internal carotid artery of the sham operation group but the middle cerebral artery was not ligated. A focal cerebral ischemia/reperfusion model was established by inserting thread into the right middle cerebral artery.The model rats in the edaravone groups were given tail vein injections of edaravone at 3 mg/kg body weight after ischemia for 2 hours and reperfusion for 12 or 24 hours. Ischemia/reperfusion groups (model group) received intravenous infusion of normal saline at the same volume as the edaravone groups after ischemia for 2 hours and reperfusion for 12 or 24 hours.MAIN OUTCOME MEASURES: The volume of the ischemic region was measured by 2,3,5-triphenyltetrazolium chloride staining. Notch1 and NF-κB protein and mRNA expression were measured by immunohistochemistry and RT-PCR. Protein expression was represented by the absorbance value.RESULTS: Edaravone greatly reduced the focal infarct volume. Notch1 and NF-κB protein and mRNA expression were rapidly upregulated following cerebral ischemia/reperfusion injury in model and edaravone groups compared with the sham operation group (P < 0.01). In addition, edaravone treatment significantly upregulated Notchl expression but down-regulated NF-κB expression compared with model groups (P <0.01).CONCLUSION: Edaravone possibly protects brain tissue from ischemia/reperfusion injury by upregulating Notch1 expression and regulating NF-κB expression.