title: Cochlear pathology of long term neomycin induced deafness in cats.
abstract: The long term sequelae of hair cell destruction consequent from administration of the ototoxic aminoglycoside antibiotic, neomycin sulfate, were evaluated in histological and ultrastructural studies of cochlear morphology in cats. Complete hearing loss, as defined by an absence of brainstem evoked responses to click stimulation at 120 dB peak SPL, was induced by intramuscular injections of neomycin at 50 mg/kg body weight/day, and cochlear pathology was studied at 6 months and 1, 3 and 4 years following onset of profound deafness. In these long term ototoxicity cases the organ of Corti was collapsed and resorbed over the basal one-quarter to three-quarters of the cochlear spiral, depending on duration of deafness. Significant progressive reduction in the spiral ganglion cell population and sequential degenerative alterations in the remaining neurons were observed with increasing time elapsed after induced hearing loss. The sequence of pathological alterations in spiral ganglion neurons appeared to be: a) swelling, demyelination and degeneration of the peripheral dendrites; b) demyelination and shrinkage of the cell soma with preservation of the central axon; and c) demyelination of the central axon and degeneration of the cell perikaryon. In apical cochlear regions, severe degeneration of the spiral ganglion preceded the collapse of the tunnel of Corti and regional loss of pillar cells. Residual populations of spiral ganglion neurons were as low as 1-2% of the normal values in the most severely degenerated cochleae in the series. Light microscopic and ultrastructural studies revealed a selective survival advantage for the unmyelinated type II neurons over the myelinated type I neurons with these long survival periods. The prolonged time course and atrophic nature of these pathological alterations suggests that degeneration of spiral ganglion neurons progresses continuously following drug-induced insult to the cochlea. Some possible factors contributing to this long term progressive degeneration will be discussed.
authors: Department of Otolaryngology, Epstein Laboratory, University of California, San Francisco 94143-0526.
authors: P A
authors: PA
authors: Leake
authors: G T
authors: GT
authors: Hradek
mesh_terms: D000818:Animals; D002415:Cats; D002452:Cell Count; D003051:Cochlea / Q000187:drug effects / Q000294:innervation / Q000648:ultrastructure*; D003056:Cochlear Nerve / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D003638:Deafness / Q000139:chemically induced* / Q000473:pathology; D007273:Injections, Intramuscular; D008854:Microscopy, Electron; D009355:Neomycin / Q000633:toxicity*; D009410:Nerve Degeneration / Q000187:drug effects*; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D009355:Neomycin