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.