Marean G C, Burt J M, Beecher M D, Rubel E W
Department of Speech and Hearing Sciences, University of Washington, Seattle 98195.
Hear Res. 1993 Dec;71(1-2):125-36. doi: 10.1016/0378-5955(93)90028-y.
Behavioral detection thresholds were obtained from four starlings before, during, and after 11 days of subcutaneous injections of kanamycin. Birds were operantly conditioned to respond to pure-tones ranging in frequency from 0.25 kHz to 7 kHz using the method of constant stimuli and were tested daily for 141 days after the first injection of aminoglycoside. All four birds sustained hearing losses greater than 60 dB at frequencies from 4 kHz to 7 kHz by the end of the 11 day injection schedule. Two birds had a slight shift in threshold at 3 kHz. No change in threshold occurred for any of the birds at lower frequencies. Recovery of detection thresholds began soon after the injections ceased and continued for approximately 50 days. In all four birds there was some degree of permanent hearing loss: 5 dB to 15 dB at frequencies between 4 kHz and 6 kHz, and approximately 25 dB at 7 kHz. Scanning electron microscopy (SEM) was performed at 0 and 5 days post-injection in a separate group of starlings given the same injection schedule. Hair cell loss and damage was observed across the basal 34% to 36% of the basilar papilla. SEM in two behaviorally tested birds sacrificed 142 days after the first injection showed that there was regeneration of hair cells to populate the previously damaged region, but that disorientation of stereocilia bundles in the basal third of the basilar papilla was common. The other two behaviorally tested birds were treated with kanamycin again for 16 days beginning at 142 days after the first injection. Thresholds shifted again, but less than during the first dosing period. SEM of these birds' basilar papillae showed less hair cell loss than observed in the birds given only a single, 11 day dosing of kanamycin. This result suggests that birds may be less susceptible to the ototoxic effects of kanamycin in repeated treatments. In all four birds, the degree and position of damage observed with SEM corresponded with the extent and frequency of hearing loss.
在对四只椋鸟进行为期11天的皮下注射卡那霉素之前、期间和之后，测定了它们的行为检测阈值。采用恒定刺激法对鸟类进行操作性条件训练，使其对频率范围为0.25千赫兹至7千赫兹的纯音做出反应，并在首次注射氨基糖苷类药物后的141天内每天进行测试。在为期11天的注射期结束时，所有四只鸟在4千赫兹至7千赫兹的频率范围内听力损失均大于60分贝。两只鸟在3千赫兹处的阈值略有变化。在较低频率下，任何一只鸟的阈值都没有变化。注射停止后不久，检测阈值开始恢复，并持续约50天。在所有四只鸟中都存在一定程度的永久性听力损失：在4千赫兹至6千赫兹之间的频率处为5分贝至15分贝，在7千赫兹处约为25分贝。在另一组接受相同注射方案的椋鸟中，在注射后0天和5天进行了扫描电子显微镜（SEM）检查。在基底乳头的基部34%至36%区域观察到毛细胞损失和损伤。在首次注射后142天处死的两只经过行为测试的鸟的SEM显示，毛细胞再生以填充先前受损区域，但基底乳头基部三分之一处的静纤毛束排列紊乱很常见。另外两只经过行为测试 的鸟在首次注射后142天开始再次用卡那霉素治疗16天。阈值再次变化，但小于第一次给药期。这些鸟的基底乳头的SEM显示，毛细胞损失比仅接受单次11天卡那霉素给药的鸟少。这一结果表明，鸟类在重复治疗中可能对卡那霉素的耳毒性作用不太敏感。在所有四只鸟中，SEM观察到的损伤程度和位置与听力损失的程度和频率相对应。
