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Cool OtOprotective Ear Lumen(COOL)疗法治疗顺铂诱导的听力损失。

Cool OtOprotective Ear Lumen (COOL) Therapy for Cisplatin-induced Hearing Loss.

机构信息

Department of Otolaryngology-Head and Neck Surgery.

Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi.

出版信息

Otol Neurotol. 2021 Mar 1;42(3):466-474. doi: 10.1097/MAO.0000000000002948.

Abstract

HYPOTHESIS

Localized cooling of the external ear has a protective effect on the susceptibility to cisplatin-induced hearing loss.

BACKGROUND

We previously demonstrated significant protection from cisplatin-induced hearing loss using cool water ear canal irrigation. However, the study was limited to a single bolus injection of cisplatin and an acute time period. Here, we examined the application of localized cooling of the ear canal with repeated doses of cisplatin, over an expanded period of time, and using two methods of cooling.

METHODS

Twenty-four guinea pigs (12 male and 12 female) underwent auditory physiological testing (auditory brainstem response and distortion product otoacoustic emissions at 8-32 kHz) and pre/postadministration of cisplatin. Cisplatin (4 mg/kg i.p.) was administered in 3 weekly single injections for a total of 12 mg/kg. While anesthetized, the left ears of the guinea pigs were exposed to either cool water (22°C; ICS Water Caloric Irrigator), a cool ear bar (15°C, cooled by a Peltier device; TNM, Scion NeuroStim), or left uncooled as a sham control. The animals were tested 3 days post each dosage and 1 month post the final dose. At the end of the experiment the animals were euthanized for histological evaluation.

RESULTS

We found that hearing loss was significantly reduced, and hair cell survival greatly improved, in animals that received cooling treatments compared to cisplatin-only control animals. No significant difference was observed between the two methods of cooling.

CONCLUSION

Localized cooling of the ear canal during administration of cisplatin mitigated loss of auditory function and loss of hair cells.

摘要

假设

局部冷却外耳对顺铂诱导的听力损失的易感性具有保护作用。

背景

我们之前通过使用冷水耳道冲洗证明了对顺铂诱导的听力损失有显著的保护作用。然而,该研究仅限于单次顺铂冲击注射和急性时间周期。在这里,我们检查了在较长时间内使用两种冷却方法,通过重复给予顺铂来应用耳道局部冷却。

方法

24 只豚鼠(12 只雄性和 12 只雌性)接受听觉生理测试(8-32 kHz 的听觉脑干反应和畸变产物耳声发射)和顺铂给药前后测试。顺铂(4mg/kg,ip)每周给予 3 次单次注射,共给予 12mg/kg。豚鼠麻醉时,左侧耳朵暴露于 22°C 的冷水(ICS 水热灌洗器)、15°C 的冷耳棒(由 Peltier 装置冷却;TNM,Scion NeuroStim)或作为假对照的未冷却的左耳。动物在每次剂量后 3 天和最后一次剂量后 1 个月进行测试。实验结束时,动物被安乐死进行组织学评估。

结果

我们发现,与仅接受顺铂的对照动物相比,接受冷却治疗的动物听力损失显著减少,毛细胞存活率大大提高。两种冷却方法之间没有观察到显著差异。

结论

顺铂给药期间对耳道进行局部冷却减轻了听觉功能和毛细胞的丧失。

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