Ultrastructural changes in the albino guinea pig cochlea at different survival times following cessation of 8-day cisplatin administration.
OBJECTIVE
To investigate the effect of cisplatin administration on the ultrastructural morphology of the organ of Corti, stria vascularis and spiral ganglion.


METHODS
Forty-eight guinea pigs were treated with cisplatin by daily i.p. injection at a dose of 1.5 mg/kg for eight consecutive days. Electrocochleography was performed at various survival times after the final application of cisplatin. The cochleae were subsequently examined using electron microscopy.


RESULTS
Ultrastructural examination corroborated that, in cochlear turns showing complete loss of outer hair cells (OHCs) at the light microscopic level, OHCs were indeed missing and had been completely replaced by supporting cells. OHC loss, the number of affected OHCs and the degree of intracellular pathology in the OHCs in the 1-day, 1-week and 2-week survival groups were considerably higher than in the 4- and 8-week survival groups. All degenerated OHCs demonstrated ultrastructural features commonly associated with necrosis. No morphological signs of apoptosis were observed. Strial changes consisted of protrusion of the apical membrane of the marginal cells into the scala media, without any other histopathological changes. Intermediate-cell atrophy, apparent as translucent areas at the light microscopic level, consisted of an increase in intercellular space due to shrinkage of intermediate and marginal cells ultrastructurally. Ultrastructural examination of the spiral ganglion showed that vacuolation of the spiral ganglion cells, seen at the light microscopic level, was due to severe swelling of the mitochondria.


CONCLUSIONS
The present results corroborate our previous light microscopic findings. However, the ultrastructural results do not allow a conclusion to be drawn concerning whether the observed recovery is due to the formation of new OHCs or to (self-)repair of damaged OHCs, although the latter is less likely.
Cardinaal
Remco M
RM
Hearing Research Laboratories, Department of Otorhinolaryngology, University Medical Center Utrecht, Utrecht, The Netherlands.
De Groot
John C M J
JC
Huizing
Egbert H
EH
Smoorenburg
Guido F
GF
Veldman
Jan E
JE
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001300:Audiometry, Evoked Response; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure*; D005260:Female; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D008854:Microscopy, Electron; D009925:Organ of Corti / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D013136:Spiral Ganglion / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D013316:Stria Vascularis / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D013997:Time Factors
D000970:Antineoplastic Agents; D002945:Cisplatin