In Vitro Model of Cochlear Implant Trauma: Oto-Protection by a Combination of NAC, Dex, and Mannitol

Objectives: (1) Describe the otoprotective mechanisms involved in common otoprotective drugs (ie, NAC, dexamethasone, and mannitol). (2) Describe the otoprotective effect of combining these drugs to prevent hair cell (HC) losses. Methods: Cochlear explants were dissected from P‐3 rats and placed in serum‐free media. Explants were divided into 3 groups: (1) untreated controls; (2) electrode insertion trauma (EIT); (3) Tri‐therapy (L‐NAC + DXM + mannitol). Cochlea of groups 2 and 3 were implanted and HC counts, oxidative stress and cleaved caspase‐3 markers were studied in all explants post EIT. Results: There was a significant increase of HC loss in the EIT explants as opposed to control or the tri‐therapy cochlea. The implantation resulted in an increased production of the total reactive oxygen species (ROS) in both HCs and the supporting cells (SCs) of only EIT group. There is also cleaved caspase‐3 activation in EIT cochlea as compared to the control or tri‐therapy cochlea. Conclusions: The tri‐therapy combining NAC, dexamethasone, and mannitol has an otoprotective effect on survival of hair cells and support cells post–cochlear implantation. This in vitro oto‐protection needs to be tested in vivo, in an animal model of cochlear implantation trauma.