Effect of Intracochlear Brain-Derived Neurotrophic Factor on Guinea Pig Sensorineural Hearing Loss.

Abstract

ImportanceThis study investigates the potential of brain-derived neurotrophic factor (BDNF) as treatment for sensorineural hearing loss (SNHL) in a guinea pig model to potentially advance hearing restoration strategies. The correlation between oxidation-reduction (REDOX) potential in blood and perilymph is evaluated to confirm using blood as a proxy for perilymph in further study.ObjectivesTo evaluate hearing following 2 intracochlear applications of BDNF as a therapy for hearing loss. To evaluate for correlation in REDOX potential of perilymph and auditory brainstem response (ABR).Study DesignPositive-control animal preclinical study.SettingTranslational laboratory science.ParticipantsAnimal model (guinea pigs).Intervention or ExposuresSNHL was created in 15 guinea pigs using intraperitoneal cisplatin (CDDP). SNHL was confirmed via ABR testing. Left ears received 2 intracochlear applications of BDNF in varying doses, 30 days apart. Right ears received saline as controls.Main Outcome MeasuresHearing threshold was determined using ABR testing. Animals underwent terminal surgery to measure the REDOX potential in cerebrospinal fluid (CSF) and blood. Analysis of variance for repeated measures using the SPSS v27 software was employed.ResultsVariable, subtotal hearing loss was established utilizing CDDP. Animal ABR thresholds after CDDP, prior to first BDNF application, were worse than baseline. There was no improvement in hearing thresholds when treated and nontreated ears were compared. Varying doses of BDNF did not produce differences in hearing thresholds. The REDOX potential of perilymph, blood, and CSF correlate in the same animal; however, the values themselves were significantly different.Conclusions and RelevanceThere is no improvement in guinea pig hearing with 2 intracochlear applications of BDNF when applied as described in this paper. Previous work suggested possible subclinical gain with 1 application; however, with 2 applications we found no improvement. The REDOX potential of blood and CSF correlates within an animal, suggesting blood may be used as a proxy for REDOX measures in perilymph.