Otani Hiroshi, Togashi Hiroko, Jesmin Subrina, Sakuma Ichiro, Yamaguchi Taku, Matsumoto Machiko, Kakehata Hitoshi, Yoshioka Mitsuhiro
Department of Neuropharmacology, Hokkaido Graduate University School of Medicine, Sapporo 060-8638, Japan.
Eur J Pharmacol. 2005 Apr 11;512(2-3):129-37. doi: 10.1016/j.ejphar.2005.01.050.
We examined the effect of a free radical scavenger edaravone on ischemia/reperfusion-induced impairment of long-term potentiation in the perforant path-dentate gyrus synapses of the rat hippocampus, as a measure of functional outcome 4 days after transient global ischemia (2-vessel occlusion, 10 min). Edaravone (3 and 10 mg/kg, i.v.) immediately after reperfusion (Day 0) alleviated ischemia-induced impairment of long-term potentiation in a dose-related manner, whereas treatment on Day 1 or 4 after reperfusion failed to rescue the impaired long-term potentiation. Edaravone administration on Day 0 also prevented the post-ischemic increase in hydroxyl radical formation and the expression of vascular endothelial growth factor, basic fibroblast growth factor and neuronal and inducible nitric oxide synthases of the hippocampus. Thus, edaravone protected the rat hippocampus from ischemia-induced long-term potentiation impairment with a therapeutic time window, suggesting that free radical formation after ischemia/reperfusion is a pivotal trigger of neurofunctional complications after global ischemic stroke.
我们研究了自由基清除剂依达拉奉对大鼠海马穿通通路-齿状回突触中缺血/再灌注诱导的长时程增强损伤的影响，以此作为短暂性全脑缺血（双动脉闭塞，10分钟）4天后功能转归的一项指标。再灌注后即刻（第0天）静脉注射依达拉奉（3和10毫克/千克）可剂量依赖性减轻缺血诱导的长时程增强损伤，而在再灌注后第1天或第4天进行治疗则无法挽救受损的长时程增强。第0天给予依达拉奉还可预防缺血后海马中羟自由基生成增加以及血管内皮生长因子、碱性成纤维细胞生长因子、神经元型和诱导型一氧化氮合酶的表达。因此，依达拉奉在治疗时间窗内保护大鼠海马免受缺血诱导的长时程增强损伤，提示缺血/再灌注后自由基形成是全脑缺血性卒中后神经功能并发症的关键触发因素。
