McFadden Sandra L, Ding Dalian, Jiang Haiyan, Salvi Richard J
Center for Hearing and Deafness, University at Buffalo, 215 Parker Hall, Buffalo, NY 14214, USA.
Brain Res. 2004 Jan 30;997(1):40-51. doi: 10.1016/j.brainres.2003.10.031.
Ethacrynic acid (EA) is known to interact with aminoglycoside antibiotics such as gentamicin (GM). In the chinchilla, co-administration of GM and EA can produce hair cell lesions ranging from a small loss of outer hair cells (OHCs) in the base of the cochlea to complete destruction of all hair cells, depending on dosing parameters. Although hair cell loss has been characterized, little is known about the fate of efferent fibers or spiral ganglion neurons (SGNs) in this model. To study the time course of efferent fiber and SGN loss, chinchillas were injected with GM (125 mg/kg IM) followed immediately by EA (40 mg/kg IV). Estimates of efferent fiber loss and density changes were made after 3 days or 1, 2, 3, or 4 weeks of survival. Estimates of SGN loss and density changes were made after 15 days or 1, 2, 4, or 6 months of survival. Cochlear function was rapidly abolished and all cochlear hair cells were missing within 24 h after treatment. Inner hair cells (IHCs) in the middle turn of the cochlea died earlier than cells in the apex or base, and OHCs in Rows 1 and 2 died earlier than OHCs in Row 3. Degeneration of efferent nerve fibers began 3-7 days post-injection, versus 15-30 days for SGNs, and the loss of efferent fibers was essentially complete within 1 month, versus 2-4 months for SGNs. The rapid time course of efferent fiber and SGN loss in the chinchilla may make it a practical model for studying mechanisms of neural loss and survival in the mammalian inner ear.
已知依他尼酸（EA）会与庆大霉素（GM）等氨基糖苷类抗生素相互作用。在栗鼠中，联合使用GM和EA会导致毛细胞损伤，损伤程度从耳蜗底部外毛细胞（OHC）少量缺失到所有毛细胞完全破坏不等，具体取决于给药参数。尽管已经对毛细胞损失进行了表征，但在该模型中，关于传出纤维或螺旋神经节神经元（SGN）的命运却知之甚少。为了研究传出纤维和SGN损失的时间进程，给栗鼠注射GM（125mg/kg，肌肉注射），随后立即静脉注射EA（40mg/kg）。在存活3天或1、2、3或4周后，对传出纤维损失和密度变化进行评估。在存活15天或1、2、4或6个月后，对SGN损失和密度变化进行评估。治疗后24小时内，耳蜗功能迅速丧失，所有耳蜗毛细胞均缺失。耳蜗中部的内毛细胞（IHC）比顶部或底部的细胞死亡更早，第1排和第2排的OHC比第3排的OHC死亡更早。传出神经纤维变性在注射后3 - 7天开始，而SGN为15 - 30天，传出纤维损失在1个月内基本完成，而SGN为2 - 4个月。栗鼠中传出纤维和SGN损失的快速时间进程可能使其成为研究哺乳动物内耳神经损失和存活机制的实用模型。
