Selective loss of inner hair cells and type-I ganglion neurons in carboplatin-treated chinchillas - Mechanisms of damage and protection
Selective loss of inner hair cells and type-I ganglion neurons in carboplatin-treated chinchillas - Mechanisms of damage and protection
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DOI：
10.1111/j.1749-6632.1999.tb08640.x
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发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
Mueller, M
中科院分区：
文献类型：
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作者：
Ding, DL;Wang, J;Mueller, M
卡铂优先破坏内毛细胞（IHC）和I型螺旋神经节神经元，而保留外毛细胞（OHC）。IHC和I型神经节细胞的丧失与复合动作电位（CAP）的显著降低相关。然而，耳蜗颤噪（CM）电位和畸变产物耳声发射（DPOAEs）保持正常，表明OHC功能完好。在前庭系统中，卡铂选择性地破坏I型毛细胞及其传入神经元。I型前庭毛细胞及其传入终末的损伤与冷、热刺激引起的眼球震颤的显著抑制有关。组织化学研究显示，卡铂治疗后不久，IHC中琥珀酸脱氢酶（SDH）染色迅速减少，卡铂治疗后至少1个月，存活的IHC中的染色强度仍处于抑制状态。这些结果表明，卡铂抑制了存活的IHC的代谢功能。一些证据表明，自由基可能有助于卡铂诱导的感觉细胞损伤。脑内输注L-丁硫氨酸-[S，R]-亚砜亚胺（BSO）可消耗细胞内谷胱甘肽（GSH），增加IHC和OHC损失。之前的体外研究表明，神经营养素4/5（NT-4/5）促进螺旋神经节神经元免受顺铂耳毒性的存活。在体灌注NT-4/5促进螺旋神经节神经元的存活，但不保护毛细胞。
Carboplatin preferentially destroys inner hair cells (IHCs) and type-I spiral ganglion neurons while sparing outer hair cells (OHCs). Loss of IHCs and type-I ganglion cells Is associated with a significant reduction of the compound action potential (CAP). However, the cochlear microphonic (CM) potential and distortion product otoacoustic emissions (DPOAEs) remain normal, indicating that the OHCs are functionally intact. In the vestibular system, carboplatin selectively destroys type-I hair cells and their afferent neurons. Damage of type-I vestibular hair cells and their afferent terminals is associated with significant depression of nystagmus induced by cold, caloric stimulation. Histochemical studies revealed a rapid decrease in succinate dehydrogenase (SDH) staining in IHCs soon after carboplatin treatment, and staining intensity remained depressed in surviving IHCs for at least 1 month after carboplatin treatment These results suggest that carboplatin depresses the metabolic function in surviving IHCs. Several lines of evidence suggest that free radicals may contribute to carboplatin-induced sensory cell damage. Intracochlear infusion of L-buthionine-[S,R]-sulfoximine (BSO), which depletes intracellular glutathione (GSH), increases IHC and OHC loss. Previous in vitro studies have shown that neurotrophin 4/5 (NT-4/5) promotes the survival of spiral ganglion neurons from cisplatin ototoxicity. In vivo perfusion of NT-4/5 promoted the survival of spiral ganglion neurons, but did not protect the hair cells.