Pattern of hair cell loss and delayed peripheral neuron degeneration in inner ear by a high-dose intratympanic gentamicin
Pattern of hair cell loss and delayed peripheral neuron degeneration in inner ear by a high-dose intratympanic gentamicin
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高剂量鼓室内庆大霉素导致内耳毛细胞丢失和延迟性周围神经元变性的模式
DOI：
10.1016/j.joto.2014.12.001
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发表时间：
2014-09
影响因子：
1.9
通讯作者：
Richard Salvi
中科院分区：
文献类型：
--
作者：
Fengjun Wang;Haiyan Jiang;Hong Sun;Richard Salvi
为了深入了解氨基糖苷类抗生素（AmAn）的耳毒性作用和内耳迟发性外周神经节神经元死亡，实验动物模型被广泛使用多种不同的方法，包括AmAn全身注射、AmAn和利尿剂的联合治疗或局部应用AmAn。在这些方法中，单独的全身性AmAn治疗通常会导致内耳毛细胞的不完全损伤。利尿剂与AmAn合用可完全破坏耳蜗毛细胞，但不可能损害前庭系统。只有局部应用AmAn的方法才能选择性地消除内耳的大多数感觉毛细胞。因此，AmAn局部应用更适合于耳蜗和前庭系统毛细胞完全破坏和随后的延迟性周围神经节神经元死亡的研究。在目前的研究中，豚鼠单侧接受高浓度庆大霉素（GM，40 mg/ml）通过鼓膜进入中耳腔。治疗前后分别测定听功能和前庭功能。在治疗后30天或60天定量耳蜗和前庭系统中毛细胞的损失和神经节神经元的延迟变性。结果表明，经GM治疗后，大鼠的听觉和前庭功能均完全消失。耳蜗内感觉毛细胞完全缺失，前庭终器内感觉毛细胞破坏严重。致聋后60天，迟发性螺旋神经节神经元死亡率超过50%。而前庭神经节神经元在治疗后60天未观察到明显的病理变化。这些结果表明，高浓度的庆大霉素递送到中耳腔可以破坏内耳中的大多数感觉毛细胞，随后引起迟发性螺旋神经节神经元变性。该模型可能是有用的毛细胞再生，外周听觉神经元的延迟变性，和/或前庭补偿的研究。此外，对单侧耳聋ABR记录的潜在问题和前庭代偿问题也进行了讨论。
To gain insights into the ototoxic effects of aminoglycoside antibiotics (AmAn) and delayed peripheral ganglion neuron death in the inner ear, experimental animal models were widely used with several different approaches including AmAn systemic injections, combination treatment of AmAn and diuretics, or local application of AmAn. In these approaches, systemic AmAn treatment alone usually causes incomplete damage to hair cells in the inner ear. Co-administration of diuretic and AmAn can completely destroy the cochlear hair cells, but it is impossible to damage the vestibular system. Only the approach of AmAn local application can selectively eliminate most sensory hair cells in the inner ear. Therefore, AmAn local application is more suitable for studies for complete hair cell destructions in cochlear and vestibular system and the following delayed peripheral ganglion neuron death. In current studies, guinea pigs were unilaterally treated with a high concentration of gentamicin (GM, 40 mg/ml) through the tympanic membrane into the middle ear cavity. Auditory functions and vestibular functions were measured before and after GM treatment. The loss of hair cells and delayed degeneration of ganglion neurons in both cochlear and vestibular system were quantified 30 days or 60 days after treatment. The results showed that both auditory and vestibular functions were completely abolished after GM treatment. The sensory hair cells were totally missing in the cochlea, and severely destroyed in vestibular end-organs. The delayed spiral ganglion neuron death 60 days after the deafening procedure was over 50%. However, no obvious pathological changes were observed in vestibular ganglion neurons 60 days post-treatment. These results indicated that a high concentration of gentamycin delivered to the middle ear cavity can destroy most sensory hair cells in the inner ear that subsequently causes the delayed spiral ganglion neuron degeneration. This model might be useful for studies of hair cell regenerations, delayed degeneration of peripheral auditory neurons, and/or vestibular compensation. In addition, a potential problem of ABR recording for unilateral deafness and issues about vestibular compensation are also discussed.
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影响因子：
16.1
作者：
Swan, Erin E. Leary;Mescher, Mark J.;Sewell, William F.;Tao, Sarah L.;Borenstein, Jeffrey I.
通讯作者：
Borenstein, Jeffrey I.
影响因子：
3.7
作者：
Ding D;Qi W;Yu D;Jiang H;Han C;Kim MJ;Katsuno K;Hsieh YH;Miyakawa T;Salvi R;Tanokura M;Someya S
通讯作者：
Someya S
影响因子：
2.8
作者：
Shibata, Seiji B.;Budenz, Cameron L.;Bowling, Sara A.;Pfingst, Bryan E.;Raphael, Yehoash
通讯作者：
Raphael, Yehoash
DOI：
10.1007/s101620020004
发表时间：
2002-03-01
影响因子：
2.4
作者：
Ding, DL;McFadden, SL;Salvi, RJ
通讯作者：
Salvi, RJ
DOI：
10.1201/9781420038736-18
发表时间：
2001-05
期刊：
--
影响因子：
--
作者：
D. Ding;S. McFadden;R. Salvi
通讯作者：
D. Ding;S. McFadden;R. Salvi