An efficient strategy for establishing a model of sensorineural deafness in rats

• Published in: Neural regeneration research 2015-10, Vol.10 (10), p.1683-1689
• Main Authors: Ma, Long, Yi, Hai-Jin, Yuan, Fen-Qian, Guo, Wei-Wei, Yang, Shi-Ming
• Format: Article
• Language: English
• Subjects: Care and treatment; Deafness; Diagnosis; Diuretics; Drug dosages; Ears & hearing; nerve regeneration; sensorineural deafness; kanamycin; furosemide; ototoxic drug; spiral ganglion cells; hair cell; neural regeneration; Scanning electron microscopy; 免疫细胞化学; 听性脑干反应; 大鼠模型; 氨基糖苷类抗生素; 硫酸卡那霉素; 神经节细胞; 耳蜗毛细胞; 药物应用
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.153704

Ototoxic drugs can be used to produce a loss of cochlear hair cells to create animal models of deafness. However, to the best of our knowledge, there is no report on the establishment of a rat deafness model through the combined application of aminoglycosides and loop diuretics. The aim of this study was to use single or combined administration of furosemide and kanamycin sulfate to establish rat models of deafness. The rats received intravenous injections of different doses of furosemide and/or intramuscular injections of kanamycin sulfate. The auditory brainstem response was measured to determine the hearing threshold after drug application. Immunocytochemistry and confocal microscopy were performed to evaluate inner ear morphology. In the group receiving combined administration of furosemide and kanamycin, the auditory brainstem response threshold showed significant elevation 3 days after administration, higher than that produced by furosemide or kanamycin alone. The hair cells showed varying degrees of injury, from the apical turn to the basal turn of the cochlea and from the outer hair cells to the inner hair cells. The spiral ganglion cells maintained a normal morphology during the first week after the hair cells completely disappeared, and then gradually degenerated. After 2 months, the majority of spiral ganglion cells disappeared, but a few remained. These findings demonstrate that the combined administration of furosemide and kanamycin has a synergistic ototoxic effect, and that these drugs can produce hair cell loss and hearing loss in rats. These findings suggest that even in patients with severe deafness, electronic cochlear implants may partially restore hearing.