Aminoglycosides (AG) antibiotics are a common treatment for recurrent infections in cystic fibrosis (CF) patients. AGs are highly ototoxic, resulting in a range of auditory dysfunctions. It was recently shown that the acoustic startle reflex (ASR) can assess behavioral evidence of hyperacusis and tinnitus in an amikacin cochleotoxicity mouse model. The goal of this study was to establish if tobramycin treatment led to similar changes in ASR behavior and to establish whether ebselen can prevent the development of these maladaptive neuroplastic symptoms. CBA/Ca mice were divided into three groups: Group 1 served as a control and did not receive tobramycin or ebselen, Group 2 received tobramycin (200 mg/kg/s.c.) and the vehicle (DMSO/saline/i.p.) daily for 14 continuous days, and Group 3 received the same dose/schedule of tobramycin as Group 2 and ebselen at (20 mg/kg/i.p.). Auditory brainstem response (ABR) and ASR hearing assessments were collected at baseline and 2, 6, 10, 14, and 18 weeks from the start of treatment. ASR tests included input/output (I/O) functions which assess general hearing and hyperacusis, and Gap-induced prepulse inhibition of the acoustic startle (GPIAS) to assess tinnitus. At 18 weeks, histologic analysis showed predominantly normal appearing hair cells and spiral ganglion neuron (SGN) synapses. Following 14 days of tobramycin injections, 16 kHz thresholds increased from baseline and fluctuated over the 18-week recovery period. I/O functions revealed exaggerated startle response magnitudes in 50% of mice over the same period. Gap detection deficits, representing behavioral evidence of tinnitus, were observed in a smaller subset (36%) of animals. Interestingly, increases in ABR wave III/wave I amplitude ratios were observed. These tobramycin data corroborate previous findings that AGs can result in hearing dysfunctions. We show that a 14-day course of tobramycin treatment can cause similar levels of hearing loss and tinnitus, when compared to a 14-day course of amikacin, but less hyperacusis. Evidence suggests that tinnitus and hyperacusis might be common side effects of AG antibiotics.

中文翻译：

---

妥布霉素耳蜗毒性小鼠模型中耳鸣和听觉过敏的发展。

氨基糖苷类 (AG) 抗生素是治疗囊性纤维化 (CF) 患者复发性感染的常用药物。AG 具有高度耳毒性，会导致一系列听觉功能障碍。最近表明，在阿米卡星耳蜗毒性小鼠模型中，听觉惊跳反射 (ASR) 可以评估听觉过敏和耳鸣的行为证据。本研究的目的是确定妥布霉素治疗是否会导致 ASR 行为的类似变化，并确定依布硒啉是否可以预防这些适应不良的神经可塑性症状的发展。CBA/Ca 小鼠分为三组：第 1 组作为对照，不接受妥布霉素或依布硒，第 2 组每天接受妥布霉素 (200 mg/kg/sc) 和载体 (DMSO/盐水/ip) 连续 14天，第 3 组接受与第 2 组相同剂量/时间表的妥布霉素和依布硒啉 (20 mg/kg/ip)。在基线和治疗开始后 2、6、10、14 和 18 周收集听觉脑干反应 (ABR) 和 ASR 听力评估。ASR 测试包括用于评估一般听力和听觉过敏的输入/输出 (I/O) 功能，以及用于评估耳鸣的间隙诱导的声惊吓前脉冲抑制 (GPIAS)。在 18 周时，组织学分析显示主要是正常出现的毛细胞和螺旋神经节神经元 (SGN) 突触。注射妥布霉素 14 天后，16 kHz 阈值从基线增加，并在 18 周恢复期内波动。I/O 功能显示，在同一时期，50% 的小鼠出现了夸大的惊吓反应幅度。间隙检测缺陷，在较小的动物子集 (36%) 中观察到代表耳鸣的行为证据。有趣的是，观察到 ABR 波 III/波 I 幅度比的增加。这些妥布霉素数据证实了先前的发现，即 AG 可导致听力功能障碍。我们表明，与阿米卡星 14 天疗程相比，妥布霉素 14 天疗程可导致相似程度的听力损失和耳鸣，但听觉过敏较少。有证据表明耳鸣和听觉过敏可能是 AG 抗生素的常见副作用。我们表明，与阿米卡星 14 天疗程相比，妥布霉素 14 天疗程可导致相似程度的听力损失和耳鸣，但听觉过敏较少。有证据表明耳鸣和听觉过敏可能是 AG 抗生素的常见副作用。我们表明，与阿米卡星 14 天疗程相比，妥布霉素 14 天疗程可导致相似程度的听力损失和耳鸣，但听觉过敏较少。有证据表明耳鸣和听觉过敏可能是 AG 抗生素的常见副作用。