Wanamaker H H, Gruenwald L, Damm K J, Ogata Y, Slepecky N
Department of Bioengineering and Neuroscience, Institute for Sensory Research, Syracuse University, New York, USA.
Am J Otol. 1998 Mar;19(2):170-9.
To test the relative dose-related cochlear and vestibular ototoxicity produced by transtympanically injected gentamicin in the Mongolian gerbil.
Transtympanic gentamicin is gaining favor as a relatively noninvasive treatment for Meniere's disease (MD). Few basic science studies exist regarding the vestibular and cochlear toxicities and dosage and administration schedules, however. The absence of standardized procedures and use of different species as animal models may account for the variable outcomes and lack of agreement found in the literature.
Histologic evaluation was performed on inner ears from Mongolian gerbils to study vestibular and cochlear damage. Comparisons were made between animals receiving single (1x) and five (5x) daily injections of gentamicin/gelfoam slurry and similarly injected (saline/gelfoam) and noninjected controls.
Two weeks after injection, qualitative and quantitative changes were seen in posterior cristae hair cells in the 1x and 5x gentamicin injected groups. Statistically significant decreases in hair cells were seen when 5x injected ears were compared with 1x injected ears and when 1x injected ears were compared with control ears. When damage was observed in the posterior crista sensory cells, damage was also seen in cochlear hair cells.
Our results suggest that in the gerbil, gentamicin is ototoxic but not selectively vestibulotoxic. In general, increasing the number of transtympanic injections increases the damage to sensory hair cells in both the posterior crista and the cochlea. A variation in interanimal susceptibility to ototoxic effects exists, but the amount of damage is consistent in both cochlear and vestibular hair cells from the same animal.
测试经鼓膜注射庆大霉素对蒙古沙鼠产生的与剂量相关的相对耳蜗和前庭耳毒性。
经鼓膜注射庆大霉素作为梅尼埃病（MD）的一种相对非侵入性治疗方法正受到青睐。然而，关于前庭和耳蜗毒性以及剂量和给药方案的基础科学研究很少。缺乏标准化程序以及使用不同物种作为动物模型可能导致文献中结果的差异和缺乏一致性。
对蒙古沙鼠的内耳进行组织学评估，以研究前庭和耳蜗损伤。比较接受单次（1x）和每日五次（5x）庆大霉素/明胶海绵混悬液注射的动物与同样注射（生理盐水/明胶海绵）和未注射的对照组。
注射后两周，在单次和五次注射庆大霉素的组中，后半规管毛细胞出现了定性和定量变化。将五次注射组的耳朵与单次注射组的耳朵以及单次注射组的耳朵与对照组的耳朵进行比较时，毛细胞数量有统计学意义的减少。当在后半规管感觉细胞中观察到损伤时，耳蜗毛细胞也出现了损伤。
我们的结果表明，在沙鼠中，庆大霉素具有耳毒性，但并非选择性前庭毒性。一般来说，增加经鼓膜注射的次数会增加后半规管和耳蜗中感觉毛细胞的损伤。动物之间对耳毒性作用的易感性存在差异，但同一动物的耳蜗和前庭毛细胞的损伤程度是一致的。
