A systemic gentamicin pathway across the stria vascularis

Hear Res. 2008 Jan;235(1-2):114-24. doi: 10.1016/j.heares.2007.10.010. Epub 2007 Nov 17.


The mechanism(s) by which systemically-administered aminoglycosides enter the cochlea remain poorly understood. To elucidate which mechanisms may be involved, we co-administered different molar ratios of gentamicin and fluorescent gentamicin (GTTR) to mice in three different regimens: (1) gentamicin (150, 300 or 600mg/kg) containing a constant 300:1 molar ratio of gentamicin:GTTR; (2) 300mg/kg gentamicin containing a variable molar ratio of gentamicin:GTTR (150:1-600:1), or (3) an increasing dose of gentamicin (150-900mg/kg), each dose containing 1.7mg/kg GTTR. Three hours later, cochleae were fixed and examined by confocal microscopy. First, increasing doses of a constant molar ratio of gentamicin:GTTR, resulted in increasing intensities of GTTR fluorescence in hair cells and strial tissues. Second, a fixed gentamicin dose with increasing molar dilution of GTTR led to decreasing GTTR fluorescence in hair cells and strial tissues. Third, a fixed GTTR dose with increasing molar dilution by gentamicin led to decreased GTTR uptake in hair cells and marginal cells, but not intra-strial tissues and capillaries. Thus, only hair cell and marginal cell uptake of GTTR is competitively inhibited by gentamicin, suggesting that a regulatable barrier for gentamicin entry into endolymph exists at the interface between marginal cells, the intra-strial space and intermediate cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / metabolism*
  • Blood-Brain Barrier / metabolism
  • Dose-Response Relationship, Drug
  • Endolymph / metabolism
  • Fluorescent Dyes / metabolism
  • Gentamicins / administration & dosage
  • Gentamicins / metabolism*
  • Hair Cells, Auditory / metabolism*
  • Injections, Subcutaneous
  • Kidney / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Stria Vascularis / metabolism*
  • Xanthenes / metabolism


  • Anti-Bacterial Agents
  • Fluorescent Dyes
  • Gentamicins
  • Xanthenes
  • Texas red