title: Kanamycin-furosemide ototoxicity in the mouse cochlea: a 3-dimensional analysis.
abstract: OBJECTIVE
  Administration of an aminoglycoside antibiotic and loop diuretic causes damage to hair cells in the organ of Corti, resulting in their death and the death of their corresponding spiral ganglion neurons. While this phenomenon has been studied previously, analysis of its effects in the whole cochlea has not been reported. The authors sought to evaluate the effects of a combination dose of kanamycin and furosemide in mice cochlea using an imaging system and computer analysis that allowed for nondestructive, whole-cochlea visualization.
  
  
  METHODS
  Study using an animal model.
  
  
  METHODS
  Cochlear analysis laboratory.
  
  
  METHODS
  Five mice received kanamycin and furosemide and 3 mice received saline. Cochleas were harvested and imaged with scanning thin-sheet laser imaging microscopy (sTSLIM) to analyze sensory cells and cochlea structures.
  
  
  RESULTS
  The drug-treated animals showed substantial loss of inner hair cells and complete outer hair cell loss. All treated mice showed spiral ganglion neuron loss with fewer neurons than control animals and decreased cell density in the middle turn of the cochlea. The spiral ligament and spiral limbus in the treated animals also showed a decrease in fibrocyte cell density in the middle to apical portion of the cochlea. The stria vascularis appeared normal in all animals.
  
  
  CONCLUSIONS
  Imaging methods that allow for whole-cochlea analysis provide insight into changes that occur in the cochlea after ototoxic insult. Trends that may not be apparent in cross-section samples of the cochlea can be observed. Computer analysis of these trends allows them to be assessed accurately.
authors.affiliation: Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Schmitz
authors.forename: Shane B
authors.initials: SB
authors.lastname: Johnson
authors.forename: Peter A
authors.initials: PA
authors.lastname: Santi
mesh_terms: D000818:Animals; D003051:Cochlea / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000648:ultrastructure; D015834:Cochlear Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging; D004195:Disease Models, Animal; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional; D007279:Injections, Subcutaneous; D007612:Kanamycin / Q000494:pharmacology / Q000633:toxicity*; D051379:Mice; D008808:Mice, Inbred CBA; D018613:Microscopy, Confocal / Q000379:methods; D009925:Organ of Corti / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D011859:Radiography; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D014463:Ultrasonography
chemical_list: D007612:Kanamycin; D005665:Furosemide
keywords: TSLIM; cell count; furosemide; hair cell; kanamycin; organ of Corti; sTSLIM; spiral ganglion neuron; spiral ligament; spiral limbus