Edaravone protects the vestibular periphery from free radical-induced toxicity in response to perilymphatic application of (+/-)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid.
Edaravone protects the vestibular periphery from free radical-induced toxicity in response to perilymphatic application of (+/-)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid.
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依达拉奉 (Edaravone) 保护前庭外周免受自由基诱导的毒性反应，以响应外淋巴应用 (I-)-α-氨基-3-羟基-5-甲基-异恶唑-4-丙酸。
DOI：
10.1016/j.ejphar.2006.10.030
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发表时间：
2007
影响因子：
5
通讯作者：
H. Yamashita
中科院分区：
文献类型：
--
作者：
H. Shimogori;Tsuyoshi Takemoto;T. Mikuriya;H. Yamashita
用注射泵向豚鼠颅内注入（±）-α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA），诱发外周前庭功能障碍。动物全身或局部给予依达拉奉。在全身应用组中，动物在AMPA输注后每天给予依达拉奉一次，持续7天。局部应用组于AMPA滴注后即刻、12 h、24 h将依达拉奉浸泡的明胶海绵置于圆窗膜上。AMPA输注后观察到自发性眼球震颤。AMPA输注后24 h进行4-羟基-2-壬烯醛（4-HNE）的免疫组织化学，4-HNE是自由基诱导的脂质过氧化反应的标志物。此外，在AMPA输注后1周进行冷热试验以评估前庭功能。两组动物均显示自发性眼球震颤减少，但结果不显著。在AMPA输注后12小时内用依达拉奉局部治疗的动物显示外半规管壶腹感觉上皮细胞形态正常，对热量试验反应良好。4-在这些动物的感觉上皮HNE免疫反应性是非常低的。相比之下，未处理的动物和AMPA输注后24 h全身或局部给予依达拉奉的动物显示形态学毛细胞损伤、热量反应降低和感觉上皮中显著的4-HNE免疫反应性。这些结果表明，损伤后12小时内局部应用依达拉奉可保护前庭外周免受AMPA脑内输注引起的自由基诱导毒性。
Intracochlear infusion of (±)-α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) was performed with a syringe pump in guinea pigs, and peripheral vestibular dysfunction was induced. Animals were administered edaravone systemically or topically. In the systemic application group, animals were administered edaravone once a day for 7 days after AMPA infusion. In the topical application group, edaravone-soaked gelfoam was placed on the round window membrane just after, 12 h after or 24 h after AMPA infusion. Spontaneous nystagmus was observed after AMPA infusion. Immunohistochemistry for 4-hydroxy-2-nonenal (4-HNE), a marker of free radical-induced lipid peroxidation, was performed 24 h after AMPA infusion. In addition, caloric tests were performed to evaluate vestibular function 1 week after AMPA infusion. Animals in both groups showed decreased spontaneous nystagmus, but results were not significant. Animals treated topically with edaravone within 12 h of AMPA infusion showed normal morphology of the ampullar sensory epithelia of the lateral semicircular canals and showed a good response to the caloric tests. 4-HNE immunoreactivity in the sensory epithelia was very low in these animals. In contrast, untreated animals and animals treated with edaravone systemically or topically 24 h after AMPA infusion showed morphologic hair cell damage, reduced caloric response and remarkable 4-HNE immunoreactivity in the sensory epithelia. These results indicate that topical application of edaravone within 12 h after damage protects the vestibular periphery from free radical-induced toxicity in response to intracochlear infusion of AMPA.
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影响因子：
5
作者：
Tanaka, K;Takemoto, T;Yamashita, H
通讯作者：
Yamashita, H
影响因子：
5
作者：
Takemoto, T;Sugahara, K;Yamashita, H
通讯作者：
Yamashita, H
影响因子：
5
作者：
Horiike, O;Shimogori, H;Yamashita, H
通讯作者：
Yamashita, H
(±)-α-氨基-3-羟基-5-甲基-异恶唑-4-丙酸 (AMPA) 诱导的外周前庭障碍。
DOI：
--
发表时间：
2004
期刊：
Neuroscience Letters 371
影响因子：
--
作者：
Shimogori H;et al.
通讯作者：
et al.