Molecular mechanisms underlying otoprotection by Taurodeoxycholic acid for cochlear implant trauma

Submitted by:

Dimitri Godur
University of Miami Miller School of Medicine

Presenter(s):

Dimitri A. Godur

Abstract

Background: There is a growing need to develop prophylactic and therapeutic interventions to prevent loss of residual hearing post-cochlear implantation. During cochlear implantation, the initiation of the electrode insertion trauma (EIT) triggers the activation of oxidative stress, apoptosis and inflammatory pathways that can damage sensory cells and consequently lead to the loss of residual hearing. Preserving these sensory cells by blocking the activation of these host pathways can improve hearing preservation and allows implanted individuals to benefit from better hearing outcomes. The aim of this study was to investigate the effect of Taurodeoxycholic acid (TDCA) on the preservation of the residual hearing in a preclinical animal model of cochlear implantation.

Method: Animals were divided into various groups. In first group, animals were implanted unilaterally. In second group, TDCA was applied on the round window membrane before cochlear implantation followed by insertion of the electrode. The animals in third group served as vehicle control whereas naïve animals that were not subjected to treatment with TDCA and cochlear implantation served as the control group. Contralateral ear from each group also served as the control group. Hearing thresholds of animals in each group were determined by auditory brainstem recordings (ABRs). Cochleae harvested from animals in each group was subjected to histopathological examination to determine pathological manifestations. The organ of Corti was dissected and stained with FITC phalloidin to visualize and count the number of hair cells.

Results: Hearing thresholds were significantly lower after TDCA application than in the EIT group. The organ of Corti harvested from cochlea of implanted and TDCA treated animals subject showed a significantly higher number of hair cells after immunostaining compared to implanted animal alone. The molecular mechanisms behind otoprotection involved abrogation of activation of oxidative stress and caspase pathways.

Conclusion: The result of the present study suggests that TDCA provides otoprotection against cochlear implant trauma and can be explored for developing effective interventions. The availability of new interventions to prevent electrode insertion trauma holds great potential to promote hearing preservation and expanding indications of cochlear implantation.

Objectives

To determine the efficacy of Taurodeoxycholic acid (TDCA) to provide otoprotection for cochlear implant trauma.

To determine whether Taurodeoxycholic acid (TDCA) promotes sensory cell preservation following cochlear implantation.

To decipher the molecular mechanisms by which provides Taurodeoxycholic acid (TDCA) otoprotection for cochlear implant trauma.