Leake P A, Hradek G T, Rebscher S J, Snyder R L
Department of Otolaryngology, Epstein Laboratory, University of California San Francisco 94143-0732.
Hear Res. 1991 Aug;54(2):251-71. doi: 10.1016/0378-5955(91)90120-x.
Ten newborn kittens were deafened by systemic administration of neomycin sulfate. Profound hearing losses were documented by ABR and FFR (500 Hz) testing. At 9-17 weeks of age, the young deafened cats were unilaterally implanted with a multichannel scala tympani electrode. Six of the animals were chronically stimulated at 6 dB above electrically evoked ABR thresholds for 1 h/day for periods of 1 month or 3 months. Stimuli were charge-balanced biphasic pulses (200 microseconds/phase, 30 pps.) The remaining 4 cats underwent identical deafening and implantation schedules but were not stimulated. Results indicate that administration of neomycin in neonatal cats induced degeneration of hair cells and spiral ganglion cell loss that was bilaterally symmetrical between the two cochleas of each individual animal, although there was variation between animals in the severity of the ototoxic drug effect. In animals receiving passive (unstimulated) implants, morphometric analysis of spiral ganglion cell density showed no significant difference in ganglion cell survival between the implanted cochleas and the contralateral control ears. In contrast, animals that were chronically stimulated for 3 months showed significantly better neuronal survival in implanted and stimulated cochleas as compared to contralateral deafened control ears. The induced conservation of spiral ganglion neurons was observed consistently within the basal cochlear region near the stimulating electrodes. In more apical regions there was no significant difference between the stimulated and control cochleas. The mechanisms underlying this selective conservation of spiral ganglion neurons induced by chronic intracochlear electrical stimulation are uncertain. Since no comparable chronic stimulation studies have been conducted in adults, it is not known whether similar conservation effects could be induced in mature animals.
十只新生小猫通过全身注射硫酸新霉素致聋。通过听性脑干反应(ABR)和频率跟随反应(FFR,500赫兹)测试记录到严重听力损失。在9至17周龄时,对这些致聋幼猫进行了多通道鼓阶电极单侧植入。其中六只动物在高于电诱发ABR阈值6分贝的强度下进行慢性刺激,每天刺激1小时,持续1个月或3个月。刺激采用电荷平衡双相脉冲(每相200微秒,30次/秒)。其余4只猫经历相同的致聋和植入程序,但未接受刺激。结果表明,新生猫注射新霉素会导致毛细胞变性和螺旋神经节细胞丢失,且每只动物的两个耳蜗之间呈双侧对称,尽管不同动物之间耳毒性药物作用的严重程度存在差异。在接受被动(未刺激)植入的动物中,对螺旋神经节细胞密度的形态计量学分析显示,植入耳蜗与对侧对照耳之间的神经节细胞存活率无显著差异。相比之下,与对侧致聋对照耳相比,接受3个月慢性刺激的动物在植入并受刺激的耳蜗中显示出明显更好的神经元存活率。在刺激电极附近的耳蜗基部区域持续观察到螺旋神经节神经元的诱导性保存。在更靠近顶部的区域,受刺激耳蜗与对照耳蜗之间没有显著差异。慢性耳蜗内电刺激诱导螺旋神经节神经元选择性保存的潜在机制尚不清楚。由于尚未在成体动物中进行类似的慢性刺激研究,因此尚不清楚在成熟动物中是否能诱导出类似的保存效应。