Neurotrophins prevent spiral ganglion neuron (SGN) degeneration in animal models of ototoxin-induced
deafness and may be used in the future to improve the hearing of
cochlear implant patients. It is increasingly common for patients with residual hearing to undergo
cochlear implantation. However, the effect of
neurotrophin treatment on acoustic hearing is not known. In this study,
brain-derived neurotrophic factor (
BDNF) was applied to the round window membrane of adult guinea pigs for 4 weeks using a
cannula attached to a mini-osmotic pump. SGN survival was first assessed in ototoxically deafened guinea pigs to establish that the delivery method was effective. Increased survival of SGNs was observed in the basal and middle cochlear turns of deafened guinea pigs treated with
BDNF, confirming that delivery to the cochlea was successful. The effects of
BDNF treatment in animals with normal hearing were then assessed using distortion product otoacoustic emissions (DPOAEs), pure tone, and click-evoked auditory brainstem responses (ABRs). DPOAE assessment indicated a mild deficit of 5 dB SPL in treated and control groups at 1 and 4 weeks after
cannula placement. In contrast, ABR evaluation showed that
BDNF lowered thresholds at specific frequencies (8 and 16 kHz) after 1 and 4 weeks posttreatment when compared to the control cohort receiving
Ringer's solution. Longer treatment for 4 weeks not only widened the range of frequencies ameliorated from 2 to 32 kHz but also lowered the threshold by at least 28 dB SPL at frequencies ≥16 kHz.
BDNF treatment for 4 weeks also increased the amplitude of the ABR response when compared to either the control cohort or prior to treatment. We show that
BDNF applied to the round window reduces auditory thresholds and could potentially be used clinically to protect residual hearing following
cochlear implantation.