Avian cochlear hair cell regeneration: Stereological analyses of damage and recovery from a single high dose of gentamicin
Avian cochlear hair cell regeneration: Stereological analyses of damage and recovery from a single high dose of gentamicin
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DOI：
10.1016/0378-5955(95)00190-5
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发表时间：
1995-12-01
期刊：
影响因子：
2.8
通讯作者：
Rubel, EW
中科院分区：
文献类型：
--
作者：
Janas, JD;Cotanche, DA;Rubel, EW
在鸟类中，已经有确凿的证据证明声损伤后毛细胞的再生。以前的氨基糖苷类耳毒性研究通常使用5-10天的药物疗程来损伤耳蜗并触发再生，这种长期损伤阻止了对早期再生事件的分析。为了确定单次高剂量注射氨基糖苷类庆大霉素后会发生多大的损伤以及如何恢复，白色来航鸡被给予单次高剂量的庆大霉素（100 mg/kg）。研究了三个注射后存活组和年龄匹配的对照组：短期（3-5天）、中期（2周）和长期（5周）。处死后，解剖耳蜗并进行扫描电子显微镜检查。应用体视学技术，对每组4-7只鸡的耳蜗近端沿着50%的耳蜗毛细胞计数进行定量分析，在药物注射后3-5天观察到不同程度的损伤。所有雏鸡耳蜗近端20%的毛细胞全部丢失。这种完全的毛细胞损失可以延伸到耳蜗的50%。未成熟的毛细胞在第3天可首先通过其未成熟的静纤毛来识别，未成熟的毛细胞存在于已剥脱天然毛细胞的区域和发生部分损失的区域中的数量最多。有趣的是，未成熟的毛细胞也偶尔出现在邻近区域，其中没有明显的天然毛细胞损失。两周的幸存者表现出在毛细胞数量的升高相比，在持续损害的区域和紧邻区域的控制。这种升高意味着毛细胞的过度产生可能是再生反应的一部分。损伤后5周，毛细胞数量接近对照组。
Hair cell regeneration after acoustic trauma has been conclusively documented in birds. Previous studies of aminoglycoside ototoxicity have typically used 5-10 day courses of drug to damage the cochlea and trigger regeneration, This long-term lesion prevented analysis of the early events of regeneration. We set out to determine how much damage would occur and how recovery would proceed after a single high-dose injection of the aminoglycoside gentamicin.White Leghorn chicks were given a single high dose of gentamicin (100 mg/kg). Three post-injection survival groups with age-matched controls were studied: short-term (3-5 days), intermediate-term (2 weeks) and long-term (5 weeks). After sacrifice, cochleae were dissected and processed for scanning electron microscopy. Using stereological techniques, a quantitative analysis of cochlear hair cell counts along the proximal 50% of the cochlea was performed from scanning electron micrographs on 4-7 chicks from each group.Variable degrees of damage were seen 3-5 days after the drug injection. All hair cells were lost from the proximal 20% of the cochlea in all chicks. This complete hair cell loss could extend to 50% of the cochlea. Immature appearing hair cells could be first identified by their immature stereocilia at 3 days, Immature appearing hair cells were present in greatest number in regions which had been denuded of native hair cells and in regions where partial loss occurred. Interestingly, immature appearing hair cells also occasionally appeared in adjacent areas in which there was no apparent loss of native hair cells. Two-week survivors showed an elevation in hair cell number compared to controls in regions which had sustained damage and immediately adjacent regions. This elevation implies that an overproduction of hair cells might occur as part of the regeneration response. By 5 weeks after damage hair cell numbers approximated controls.