Cochlear uptake of fluorescent gentamicin in neonatal mice

Abstract

Background: Ototoxicity in neonates and premature newborns has not been well defined if prematurity is a potential risk factor of aminoglycoside ototoxicity. Unlike the functionally mature cochlea of human newborns, the murine cochlea becomes functionally mature around 2 weeks after birth. This dynamic postnatal cochlear maturation in the mouse provides a unique opportunity to study how ototoxic reagents permeate the developing blood-labyrinth barrier to reach sensory hair cells. This study was conducted to investigate if cochlear uptake of aminoglycoside is increased in neonatal mice after systemic administration of fluorescent gentamicin (gentamicin-Texas Red, GTTR).

Materials and Methods: C57Bl/6 mice were intraperitoneally injected with GTTR at postnatal 7, 21, 35 days (P7, P21, P35). Harvested cochlear and kidney tissues were either whole-mounted or cryosectioned for microscopic exam. The intensities of GTTR in the cochlear lateral wall, cochlear hair cells and renal proximal tubular cells were quantified and compared.

Results: GTTR fluorescence in the hair cells and the lateral wall (including marginal, intermediate and basal cells of the stria vascularis, and fibrocytes of the spiral ligament) was significantly higher at P7 than at P35 (p<0.01). Animals treated with Texas Red only showed negligible Texas Red fluorescence at every time point. Renal proximal tubules did not show significant differences in fluorescence intensity between different time points.

Conclusion: Prior to complete maturation of the cochlear blood-labyrinth barrier, GTTR readily permeates into strial cells, fibrocytes and sensory hair cells.