Direct administration therapy for irreversible peripheral vestibular disorder

不可逆外周前庭障碍的直接给药治疗

• 批准号: 14571621
• 负责人: SHIMOGORI Hiroaki
• 金额: $ 1.6万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571621/
• 关键词: vestibular disorder; aminoglycoside; AMPA; edaravone; CNQX; 虚血; 抗酸化剤

We evaluated the effects of edaravone, a free radical scavenger, on the vestibular disorder induced by streptomycin (SM) or AMPA1. Lesions were made in the guinea pig right inner ear by intracochlear administration of 30% SM for 24 h using osmotic pump. Systemic administration of edaravone improved vestibulo-ocular reflex gain in guinea pigs at 3 and 7 days after lesions were made. Local application of edaravone suppressed the frequency of spontaneous nystagmus observed in guinea pigs after lesions were made2. Lesions were made in the guinea pig right inner ear by infusion of AMPA (10 mM, 50 μl) for 5 min using syringe pump. After AMPA infusion, spontaneous nystagmus was observed, and simultaneous infusion of CNQX, a potent AMPA receptor antagonist, suppressed the frequency of nystagmus in a dose-dependent manner. Local application of edaravone also suppressed the nystagmus, furthermore, early (within 12 h) application of edaravone improved a response for caloric stimulation at 1 w after lesions were madeWe concluded that local application of edaravone may be one of the treatment for vestibular disorder caused by aminoglycoside or glutamate excitotoxicity

我们评估了自由基清除剂依达拉奉对链霉素（SM）或AMPA1诱导的前庭功能障碍的影响。用渗透泵将30% SM注入耳蜗内24 h，在豚鼠右内耳形成病变。全身给药依达拉奉可改善豚鼠病变后3天和7天的前庭眼反射。局部应用依达拉奉可抑制豚鼠病变后自发性眼球震颤的频率2。用注射泵滴注AMPA (10 mM, 50 μl) 5 min，在豚鼠右内耳形成病变。在AMPA输注后，观察到自发性眼球震颤，同时输注CNQX，一种有效的AMPA受体拮抗剂，以剂量依赖性的方式抑制眼球震颤的频率。局部应用依达拉奉也能抑制眼球震颤，而且早期（12小时内）应用依达拉奉可改善病变后1 w的热刺激反应。由此可见，局部应用依达拉奉可能是治疗氨基糖苷或谷氨酸兴奋毒性引起的前庭功能障碍的一种治疗方法

项目成果

Takemoto T, Sugahara K, Okuda T, Shimagori H, Yamashita H: "The clinical free radical scavenger, edaravone, protects cochlear hair cells from acoustic trauma"Eur J Pharmacol. 487. 113-116 (2004)

Takemoto T、Sugahara K、Okuda T、Shimagori H、Yamashita H：“临床自由基清除剂依达拉奉可保护耳蜗毛细胞免受声损伤”Eur J Pharmacol。

Horiike O, Shimogori H, Yamashita H: "Effect of edaravone on streptomycin-induced vestibulotoxicity in the guinea pig"Laryngoscope. (in press).

Horiike O、Shimogori H、Yamashita H：“依达拉奉对链霉素诱导的豚鼠前庭毒性的影响”喉镜。

Takemoto T, Sugahara K, Okuda T, Shimogori H, Yamashita H: "The protective effects of edaravone on cochlear hair cell damaged induced by acoustic trauma"Toukeibujiritsusinnkei. 17. 43-46 (2003)

Takemoto T、Sugahara K、Okuda T、Shimogori H、Yamashita H：“依达拉奉对声损伤引起的耳蜗毛细胞损伤的保护作用”Toukeibujiritsusinnkei。

Osamu Horiike: "Protective effect of edaravone against streptomycin-induced vestibulotoxicity in the guinea pig"European Journal of Pharmacology. 464. 75-78 (2003)

Osamu Horiike：“依达拉奉对豚鼠链霉素诱导的前庭毒性的保护作用”欧洲药理学杂志。

Horiike O, Shimogori H, Ikeda T, Yamashita H: "Protective effect of edaravone against streptomycin-induced vestibulotoxicity in the guinea pig"Eur J Pharmacol. 464. 75-78 (2003)

Horiike O、Shimogori H、Ikeda T、Yamashita H：“依达拉奉对豚鼠链霉素诱导的前庭毒性的保护作用”Eur J Pharmacol。