Abstract
An increased number of patients with residual hearing are undergoing cochlear implantation. A subset of these experience delayed hearing loss post-implantation, and the aetiology of this loss is not well understood. Our previous studies suggest that electrical stimulation can induce damage to hair cells in organ of Corti (OC) organotypic cultures. Dexamethasone has the potential to protect residual hearing due to its multiple effects on cells and tissue (e.g., anti-inflammatory, free radical scavenger). We therefore hypothesized that dexamethasone treatment could prevent electrical stimulation induced changes in the OC. Organ of Corti explants from neonatal rats (P2–4) were cultured for 24 h with two different concentrations of dexamethasone. Thereafter, OC were subjected to a charge-balanced biphasic pulsed electrical stimulation (0.44–2 mA) for a further 24 h. Unstimulated dexamethasone-treated OC served as controls. Outcome analysis included immunohistochemical labelling of ribbon synapses, histochemical analysis of free reactive oxygen species and morphological analysis of stereocilia bundles. Overall, the protective effects of dexamethasone on electrically induced damage in cochlear explants were moderate. High-dose dexamethasone protected bundle integrity at higher current levels. Low-dose dexamethasone tended to increase ribbon density in the apical region.
Highlights
Worldwide, approximately 466 million people suffer from disabling hearing loss (World Health Organization 2019)
To screen for structural and metabolic changes induced by electrical stimulation, stimulated (Fig. 2a–c) and nonstimulated (Fig. 2d–f) organ of Corti explants were evaluated after triple labelling
The present study provides initial evidence that in vitro oxidative stress could be triggered by electrical stimulation and that the antiinflammatory and radical scavenging substance dexamethasone can be partially protective
Summary
Approximately 466 million people suffer from disabling hearing loss (World Health Organization 2019). Dexamethasone has been used for otoprotection (Bird et al 2011; Prenzler et al 2018) and acts as a catalytic radical scavenger that counteracts oxidative stress (Bas et al 2012; Sies 2015). Oxidative stress plays a major role in hearing loss induced by noise, cisplatin and treatment with aminoglycoside antibiotics (Choi and Choi 2015; Sheth et al 2017; Tavanai and Mohammadkhani 2017). We aimed to determine whether steroids have the potential to avoid or reduce the damage that is induced by electrical stimulation. Organ of Corti explants were treated in vitro with two different concentrations of dexamethasone and subsequently electrically stimulated. Since aminoglycoside toxicity and sound trauma can cause subtle changes in stereocilia, we evaluated inner hair cell stereocilia bundle morphology using stimulated emission depletion microscopy (StED) (Daudet et al 1998; Bahloul et al 2009)
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