title: Cell-specific accumulation patterns of gentamicin in the guinea pig cochlea.
abstract: Intratympanic gentamicin therapy has become a popular treatment modality for Ménière's disease (MD) through controlled elimination of vertigo spells caused by the balance organ. However, the known ototoxic properties of aminoglycosides lead to cochlear damage. In order to gain more information about cellular preferences for aminoglycoside accumulation within the cochlea, gentamicin was immuno histochemically localized by light microscopy in male guinea pigs 1 and 7 days after intratympanic application (n = 8 ears/incubation time). Differences in the gentamicin-specific cellular storage capacities were quantified by determination of the local immuno staining intensities. Gentamicin was detected in every cochlear cell type, but with spatiotemporal variability. One day after application, an intense staining reaction was found in all cell types except the spiral ganglion cells and the stria vascularis. Six days later, gentamicin staining intensities were additionally reduced in the nerve fibers and the spiral ligament. Statistic analysis revealed strong cellular associations in respect to aminoglycoside accumulation. Furthermore, associations with recorded hearing losses were identified comparing the cellular gentamicin content in the organ of Corti, in the stria vascularis, in the spiral ganglion cells and in fibrocytes of the Limbus. In the lateral wall, clear differences in cellular gentamicin accumulation were found between type I fibrocytes of the spiral ligament compared with basal and intermediate cells of the stria vascularis. This finding was unexpected as these three cell types belong to a well-developed gap-junction system which normally enables unhampered cell communication. Cellular differences in local gentamicin storage capacities, transport processes and inherent diffusion barriers are discussed.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: Ulf-Rüdiger
authors.initials: UR
authors.lastname: Heinrich
authors.affiliation: Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Schmidtmann
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Strieth
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Germany. Electronic address: kai.helling@unimedizin-mainz.de.
authors.forename: Kai
authors.initials: K
authors.lastname: Helling
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D003051:Cochlea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D006168:Guinea Pigs; D006801:Humans; D007150:Immunohistochemistry; D000069555:Injection, Intratympanic; D008297:Male; D008575:Meniere Disease / Q000188:drug therapy; D023421:Models, Animal; D014018:Tissue Distribution
chemical_list: D005839:Gentamicins