Aminoglycoside ototoxicity and hair cell ablation in the adult gerbil: A simple model to study hair cell loss and regeneration.
Aminoglycoside ototoxicity and hair cell ablation in the adult gerbil: A simple model to study hair cell loss and regeneration.
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DOI：
10.1016/j.heares.2015.03.002
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发表时间：
2015-07
期刊：
影响因子：
2.8
通讯作者：
Rivolta, Marcelo N.
中科院分区：
文献类型：
--
作者：
Abbas, Leila;Rivolta, Marcelo N.
长爪沙鼠（Meriones unguiculatus）是一种广泛用于内耳研究的动物模型。尽管其已被确定用于听觉研究，但尚未开发出针对该物种的诱导耳毒性毛细胞损伤的稳健方案。在本文中，我们证明了氨基糖苷类诱导的毛细胞损失模型的发展，使用卡那霉素加强的袢利尿剂呋塞米。有趣的是，我们发现，沙鼠是相对不敏感的庆大霉素相比，卡那霉素，布美他尼是无效的增强药物的耳毒性。我们还检查了慢性、长期毛细胞损伤后螺旋神经节的病理学。值得注意的是，在耳毒性损伤后，甚至在损伤后8个月，也很少或没有神经元损失。这与人类中常见的情况类似，在人类中，功能神经元甚至可以在毛细胞损失后持续数十年，而在大鼠，小鼠和其他小型哺乳动物中发现的快速，继发性退化形成对比。我们建议，这些因素的组合使得沙鼠耳毒性损伤诱导的毛细胞损失的一个很好的模型。我们在沙鼠模型中探索了耳毒性的不同范例。沙鼠的感觉毛细胞似乎对庆大霉素相对敏感。毛细胞损伤后螺旋神经节神经元没有明显损失。这产生了一个类似于人类病变的毛细胞损失的简单模型。该模型是研究再生策略和人工耳蜗植入的理想模型。
The Mongolian gerbil, Meriones unguiculatus, has been widely employed as a model for studies of the inner ear. In spite of its established use for auditory research, no robust protocols to induce ototoxic hair cell damage have been developed for this species. In this paper, we demonstrate the development of an aminoglycoside-induced model of hair cell loss, using kanamycin potentiated by the loop diuretic furosemide. Interestingly, we show that the gerbil is relatively insensitive to gentamicin compared to kanamycin, and that bumetanide is ineffective in potentiating the ototoxicity of the drug. We also examine the pathology of the spiral ganglion after chronic, long-term hair cell damage. Remarkably, there is little or no neuronal loss following the ototoxic insult, even at 8 months post-damage. This is similar to the situation often seen in the human, where functioning neurons can persist even decades after hair cell loss, contrasting with the rapid, secondary degeneration found in rats, mice and other small mammals. We propose that the combination of these factors makes the gerbil a good model for ototoxic damage by induced hair cell loss. We have explored different paradigms of ototoxicity in the gerbil model. The gerbil sensory hair cells seem relatively resiliant to gentamicin. Hair cell damage is not followed by significant loss of spiral ganglion neurons. This generates a simple model for hair cell loss that resembles human lesions. This model should be ideal to study regenerative strategies and cochlear implantation.
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影响因子：
64.8
作者：
Chen, Wei;Jongkamonwiwat, Nopporn;Abbas, Leila;Eshtan, Sarah Jacob;Johnson, Stuart L.;Kuhn, Stephanie;Milo, Marta;Thurlow, Johanna K.;Andrews, Peter W.;Marcotti, Walter;Moore, Harry D.;Rivolta, Marcelo N.
通讯作者：
Rivolta, Marcelo N.
影响因子：
1.4
作者：
BRUMMETT, RE;TRAYNOR, J;HIMES, D
通讯作者：
HIMES, D
影响因子：
6.1
作者：
ASTBURY, PJ;READ, NG
通讯作者：
READ, NG
DOI：
10.1023/a:1007201913730
发表时间：
2000-07-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
Dodson, HC;Mohuiddin, A
通讯作者：
Mohuiddin, A
影响因子：
1.4
作者：
ARAN, JM;DARROUZET, J
通讯作者：
DARROUZET, J