Local delivery of brain-derived neurotrophic factor on the perforated round window membrane in Guinea pigs: a possible clinical application.

Abstract

Local delivery of neurotrophic factors on the intact round window membrane (RWM) of hair cell-deprived cochleas reduces degeneration of the cochlear nerve. In an animal model of profound hearing loss, we investigated whether this otoprotective effect could be enhanced by perforation of the RWM. Such method could be highly relevant for future clinical applications. Guinea pigs were deafened by coadministration of kanamycin and furosemide. Two weeks after deafening, Gelfoam cubes infiltrated with brain-derived neurotrophic factor (BDNF) were deposited onto the RWM of the right cochlea. In the experimental condition, the RWM was perforated. Electrically evoked auditory brainstem responses (eABRs) were recorded weekly. Two or four weeks after Gelfoam placement, both left (untreated) and right (BDNF-treated) cochleas were processed for histology. In BDNF-treated cochleas, both with and without perforation, neural survival in the basal turn of the cochlea was significantly larger than in untreated cochleas. Amplitudes of electrically evoked auditory brainstem responses were larger in BDNF-treated cochleas with an RWM perforation than in those without a perforation and comparable to those of normal-hearing controls. Perforation did not lead to collateral cochlear damage. When considering clinical applications of neuroprotective agents such as BDNF, delivery on a perforated RWM seems to be a safe and effective option.