RESUMO
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.
Assuntos
Dexametasona/farmacologia , Glucocorticoides/farmacologia , Órgão Espiral/efeitos dos fármacos , Estereocílios/efeitos dos fármacos , Animais , Estimulação Elétrica , Proteínas do Olho/efeitos dos fármacos , Proteínas do Olho/metabolismo , Imuno-Histoquímica , Microscopia Confocal , Fármacos Neuroprotetores , Técnicas de Cultura de Órgãos , Órgão Espiral/metabolismo , Órgão Espiral/ultraestrutura , Ratos , Espécies Reativas de Oxigênio/metabolismo , Estereocílios/ultraestrutura , Sinapses/efeitos dos fármacos , Sinapses/metabolismoRESUMO
The first multiplication sign (.) for unit µC cm¯2·phase¯1 was not placed, which is part of the author's correction. Furthermore, the unit appears anywhere in the article.
RESUMO
Patients scheduled for cochlear implantation often retain residual hearing in the low frequencies. Unfortunately, some patients lose their residual hearing following implantation and the reasons for this are not well understood. Evidence suggests that electrotoxicity could be one of the factors responsible for this late adverse effect. Therefore, the aim of this study was to investigate the survival of spiral ganglion neurons (SGN) subjected to in vitro electrical stimulation (ES). A stimulation setup was developed to provide defined electrical fields at given points of the chamber. SGN isolated from Sprague Dawley rats (P3-4) were dissociated and cultured in the chamber for 24 h prior to biphasic, pulsed electrical field exposure for another 24 h. The current varied in the range of 0 to 2 mA and the pulse width from 10 to 400 µs. Neurite growth and survival were evaluated with respect to the charge density at the position of the cells. Non-exposed SGN cultures served as control. Charge densities below 2.2 µC·cm-2·phase-1 appeared to have no effect on SGN survival and neurite outgrowth. Charge densities above 4.9 µC·cm-2·phase-1 were detrimental to almost all cells in culture. After fitting results to a sigmoidal dose response curve, a LD50 of 2.9 µC·cm-2·phase-1 was calculated. This screening regarding survival and outgrowth of SGN provides parameters that could be used to further investigate the effect of ES on SGN and to develop possible protection strategies, which could potentially rescue residual hearing in the implanted patients.
