Time sequence of degeneration pattern in the guinea pig cochlea during cisplatin administration. A quantitative histological study.
We investigated the key tissues that are implicated in cisplatin ototoxicity within the time window during which degeneration starts. Guinea pigs were treated with cisplatin at a dose of 2 mg/kg/day for either 4, 6, or 8 consecutive days. Histological changes in the organ of Corti, the stria vascularis and the spiral ganglion were quantified at the light microscopical level. Outer hair cell (OHC) loss started between 4 and 6 days of cisplatin administration, but is only significantly different from the non-treated group after 8 days of treatment. Midmodiolar OHC counts were comparable to the cytocochleogram data. The cross-sectional area of the stria vascularis did not differ from the non-treated group, nor did an endolymphatic hydrops develop during the course of treatment. Spiral ganglion cell (SGC) densities did not decrease. After 6 days, however, detachment of the myelin sheath of the type-I SGCs was seen in the lower basal turn, whereas after 8 days it was also present in the more apically located turns. Myelin sheath detachment is the result of perikaryal shrinkage and swelling of the myelin sheath. The present study confirms that cisplatin at a daily dose of 2 mg/kg has a detrimental effect on the OHCs as well as on the type-I SGCs. These intracochlear effects occur simultaneously; OHC loss and SGC shrinkage start between the fourth and sixth day of cisplatin administration and appear to develop in parallel. At this dose, no histological effect on the stria vascularis could be observed, although previous electrophysiological experiments demonstrated a clear effect on the endocochlear potential
van Ruijven
Marjolein W M
MW
Hearing Research Laboratories, Department of Otorhinolaryngology, University Medical Center Utrecht, Room G.02.531, P.O. Box 85.500, 3508 GA Utrecht, The Netherlands. m.vanruijven@kmb.azu.nl
de Groot
John C M J
JC
Smoorenburg
Guido F
GF
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D018159:Endolymphatic Hydrops / Q000139:chemically induced; D005260:Female; D006168:Guinea Pigs; D009925:Organ of Corti / Q000187:drug effects* / Q000473:pathology; D011897:Random Allocation; D013136:Spiral Ganglion / Q000187:drug effects* / Q000473:pathology; D013316:Stria Vascularis / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
D000970:Antineoplastic Agents; D002945:Cisplatin