1. Neuronal erythropoietin overexpression is protective against kanamycin-induced hearing loss in mice.
- Author
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Bächinger D, Horvath L, Eckhard A, Goosmann MM, Honegger T, Gassmann M, Vogel J, and Naldi AM
- Subjects
- Animals, Evoked Potentials, Auditory, Brain Stem drug effects, Female, Hair Cells, Auditory drug effects, Mice, Mice, Inbred C57BL, Mice, Transgenic, Spiral Ganglion cytology, Spiral Ganglion drug effects, Anti-Bacterial Agents toxicity, Erythropoietin biosynthesis, Hearing Loss, High-Frequency chemically induced, Hearing Loss, High-Frequency prevention & control, Kanamycin toxicity, Neurons metabolism
- Abstract
Aminoglycosides have detrimental effects on the hair cells of the inner ear, yet these agents indisputably are one of the cornerstones in antibiotic therapy. Hence, there is a demand for strategies to prevent aminoglycoside-induced ototoxicity, which are not available today. In vitro data suggests that the pleiotropic growth factor erythropoietin (EPO) is neuroprotective against aminoglycoside-induced hair cell loss. Here, we use a mouse model with EPO-overexpression in neuronal tissue to evaluate whether EPO could also in vivo protect from aminoglycoside-induced hearing loss. Auditory brainstem response (ABR) thresholds were measured in 12-weeks-old mice before and after treatment with kanamycin for 15 days, which resulted in both C57BL/6 and EPO-transgenic animals in a high-frequency hearing loss. However, ABR threshold shifts in EPO-transgenic mice were significantly lower than in C57BL/6 mice (mean difference in ABR threshold shift 13.6 dB at 32 kHz, 95% CI 3.8-23.4 dB, p = 0.003). Correspondingly, quantification of hair cells and spiral ganglion neurons by immunofluorescence revealed that EPO-transgenic mice had a significantly lower hair cell and spiral ganglion neuron loss than C57BL/6 mice. In conclusion, neuronal overexpression of EPO is protective against aminoglycoside-induce hearing loss, which is in accordance with its known neuroprotective effects in other organs, such as the eye or the brain., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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