title: Time course of cochlear electrophysiology and morphology after combined administration of kanamycin and furosemide.
abstract: In animal models of deafness, administration of an aminoglycoside in combination with a loop diuretic is often applied to produce a rapid loss of cochlear hair cells. However, the extent to which surviving hair cells remain functional after such a deafening procedure varies. In a longitudinal electrocochleographical study, we investigated the variability of cochlear function between and within guinea pigs after combined administration of kanamycin and furosemide. Concurrently, histological data were obtained at 1, 2, 4 and 8 weeks after deafening treatment. The main measures in our study were compound action potential (CAP) thresholds, percentage of surviving hair cells and packing density of spiral ganglion cells (SGCs). One day after deafening treatment, we found threshold shifts widely varying among animals from 0 to 100dB. The variability decreased after 2 days, and in 18 out of 20 animals threshold shifts greater than 55dB were found 4-7 days after deafening. Remarkably, in the majority of animals, thresholds decreased by up to 25dB after 7 days indicating functional recovery. As expected, final thresholds were negatively correlated to the percentage of surviving hair cells. Notably, the percentage of surviving hair cells might be predicted on the basis of thresholds observed one day after deafening. SGC packing density, which rapidly decreased with the period after deafening treatment and correlated to the percentage of surviving inner hair cells, was not a determining factor for the CAP thresholds.
authors.affiliation: Department of Otorhinolaryngology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands. h.versnel@umcutrecht.nl
authors.forename: Huib
authors.initials: H
authors.lastname: Versnel
authors.forename: Martijn J H
authors.initials: MJ
authors.lastname: Agterberg
authors.forename: John C M J
authors.initials: JC
authors.lastname: de Groot
authors.forename: Guido F
authors.initials: GF
authors.lastname: Smoorenburg
authors.forename: Sjaak F L
authors.initials: SF
authors.lastname: Klis
mesh_terms: D000200:Action Potentials; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002470:Cell Survival; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism*; D003638:Deafness / Q000235:genetics* / Q000378:metabolism; D004594:Electrophysiology / Q000379:methods*; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D005724:Ganglia / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects; D007612:Kanamycin / Q000494:pharmacology*; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D049994:Sodium Potassium Chloride Symporter Inhibitors; D007612:Kanamycin; D005665:Furosemide