Carboplatin-induced early cochlear lesion in chinchillas.
Carboplatin preferentially damages inner hair cells (IHC) and type I spiral ganglion neurons (SGNs) in the chinchilla; however, the temporal sequence of events leading to the destruction of these structures is poorly understood. To better understand the mechanisms leading up to the destruction of IHCs and type I SGNs, we measured the activity in single auditory nerve fibers for the first 8 h following carboplatin treatment and also monitored the development of histopathologies in SGNs and IHCs using a dose of carboplatin that killed approximately 50% of the IHCs. The spontaneous discharge rate (SDR) showed a slight increase around 3 h post carboplatin followed by a significant decline at 4-5 h. The saturation driven discharge rate (DDR) showed a significant increase 1-5 h post carboplatin. These physiological changes were associated with the formation of small vacuoles in type I afferent terminals and proximal nerve fibers 1-6 h post carboplatin; signs of IHC damage were first observed around 24-48 h. Thus, the neurotoxic effects of carboplatin occur approximately a day before the IHCs are damaged. The large fluctuations in SDR and DDR that occur several hours after carboplatin treatment are most likely due to the neurotoxic effects of carboplatin.
Wang
Jian
J
School of Human Communication Disorders, Dalhousie University, 5599 Fenwick Street, B3H 1R2 Halifax, NS, Canada. wangj4@dal.ca
Ding
Dalian
D
Salvi
Richard J
RJ
D000818:Animals; D000970:Antineoplastic Agents / Q000506:poisoning*; D016190:Carboplatin / Q000506:poisoning*; D016923:Cell Death; D002682:Chinchilla; D003051:Cochlea / Q000187:drug effects / Q000473:pathology; D015834:Cochlear Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D003056:Cochlear Nerve / Q000503:physiopathology; D004558:Electric Stimulation; D004594:Electrophysiology; D006199:Hair Cells, Auditory, Inner / Q000473:pathology; D008854:Microscopy, Electron; D009474:Neurons / Q000473:pathology; D013136:Spiral Ganglion / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
D000970:Antineoplastic Agents; D016190:Carboplatin