Cochlear function after selective inner hair cell degeneration induced by carboplatin.
The ototoxicity of carboplatin, a second generation anti-cancer agent, was examined using the chinchilla as an animal model. In animals treated with a clinical therapeutic dose (400 mg/m2), the dominant degenerative change is to inner hair cells (IHCs). This is in sharp contrast to most other ototoxic agents, which damage primarily the outer hair cells (OHCs). Functional changes to the cochlea have been evaluated in carboplatin treated subjects by recording cochlear action potentials (CAP) and cochlear microphonics (CM); cochlear lesions were evaluated using scanning electron microscopy. In carboplatin treated animals, CAP thresholds to tone-pip stimuli were elevated in proportion to IHC damage in corresponding cochlear regions. In contrast, CM amplitudes and 'thresholds' remained close to normal in most cases, reflecting the preservation of OHCs in the basal turn. These results indicate a high degree of independence between the inner and outer hair cell systems in the cochlear transduction mechanism. We suggest that this species-specific preparation with selective IHC loss will provide a valuable tool for studying, separately, the role of OHCs in both afferent and efferent cochlear function.
Takeno
S
S
Department of Otolaryngology, Hospital for Sick Children, Toronto, Ontario, Canada.
Harrison
R V
RV
Ibrahim
D
D
Wake
M
M
Mount
R J
RJ
D000161:Acoustic Stimulation; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D016190:Carboplatin / Q000008:administration & dosage / Q000633:toxicity*; D002682:Chinchilla; D003051:Cochlea / Q000166:cytology / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D004594:Electrophysiology; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects*; D008855:Microscopy, Electron, Scanning; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009476:Neurons, Efferent / Q000187:drug effects / Q000502:physiology; D013045:Species Specificity
D016190:Carboplatin