Husmann K R, Morgan A S, Girod D A, Durham D
Department of Otolaryngology and the Smith Mental Retardation Research Center, University of Kansas Medical Center, Kansas City 66160-7380, USA.
Hear Res. 1998 Nov;125(1-2):109-19. doi: 10.1016/s0378-5955(98)00137-3.
Damage to inner ear sensory hair cells after systemic administration of ototoxic drugs has been documented in humans and animals. Birds have the ability to regenerate new hair cells to replace those damaged by drugs or noise. Unfortunately, the systemic administration of gentamicin damages both ears in a variable fashion with potentially confounding systemic drug effects. We developed a method of direct application of gentamicin to one cochlea of hatchling chickens, allowing the other ear to serve as a within-animal control. We tested variables including the vehicle for application, location of application, dosage, and duration of gentamicin exposure. After 5 or 28 days survival, the percent length damage to the cochlea and regeneration of hair cells was evaluated using scanning electron microscopy. Controls consisted of the opposite unexposed cochlea and additional animals which received saline instead of gentamicin. Excellent damage was achieved using gentamicin-soaked Gelfoam pledgets applied to the round window membrane. The percent length damage could be varied from 15 to 100% by changing the dosage of gentamicin, with exposures as short as 30 min. No damage was observed in control animals. Regeneration of hair cells was observed in both the base and apex by 28 days survival.
全身应用耳毒性药物后，人类和动物内耳感觉毛细胞受损的情况已有文献记载。鸟类有能力再生新的毛细胞来替代因药物或噪音而受损的毛细胞。不幸的是，庆大霉素的全身应用会以不同方式损害双耳，可能会产生混淆的全身药物效应。我们开发了一种将庆大霉素直接应用于雏鸡一个耳蜗的方法，使另一只耳朵作为动物体内对照。我们测试了包括应用载体、应用位置、剂量和庆大霉素暴露持续时间等变量。在存活5天或28天后，使用扫描电子显微镜评估耳蜗的长度损伤百分比和毛细胞的再生情况。对照组包括未暴露的对侧耳蜗以及接受生理盐水而非庆大霉素的其他动物。将庆大霉素浸泡的明胶海绵小块应用于圆窗膜可实现良好的损伤效果。通过改变庆大霉素的剂量，暴露时间短至30分钟，长度损伤百分比可在15%至100%之间变化。在对照动物中未观察到损伤。存活28天时，在耳蜗底部和顶部均观察到毛细胞再生。
