RESUMEN
OBJECTIVE: Mild therapeutic hypothermia (MTH) has been demonstrated to prevent residual hearing loss from surgical trauma associated with cochlear implant (CI) insertion. Here, we aimed to characterize the mechanisms of MTH-induced hearing preservation in CI in a well-established preclinical rodent model. APPROACH: Rats were divided into four experimental conditions: MTH-treated and implanted cochleae, cochleae implanted under normothermic conditions, MTH only cochleae and un-operated cochleae (controls). Auditory brainstem responses (ABRs) were recorded at different time points (up to 84 days) to confirm long-term protection and safety of MTH locally applied to the cochlea for 20 min before and after implantation. Transcriptome sequencing profiling was performed on cochleae harvested 24 h post CI and MTH treatment to investigate the potential beneficial effects and underlying active gene expression pathways targeted by the temperature management. RESULTS: MTH treatment preserved residual hearing up to 3 months following CI when compared to the normothermic CI group. In addition, MTH applied locally to the cochleae using our surgical approach was safe and did not affect hearing in the long-term. Results of RNA sequencing analysis highlight positive modulation of signaling pathways and gene expression associated with an activation of cellular inflammatory and immune responses against the mechanical damage caused by electrode insertion. SIGNIFICANCE: These data suggest that multiple and possibly independent molecular pathways play a role in the protection of residual hearing provided by MTH against the trauma of cochlear implantation.