Influence of the electrical stimulation on cochlear morphology and cell survival in the presence and absence of oto- and neuroprotective agents: in vitro study of novel strategies for the protection of residual hearing in patients with electric acoustic i

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Some patients with a severe hearing loss in the high frequencies can hear well in the low frequencies. To preserve their residual hearing, a novel method, i.e., electric acoustic stimulation (EAS), was developed. The damage, however, which could be possibly inflicted to the inner ear and hence to the residual hearing by electrical stimulation, has so far not been adequately studied. This is particularly important for the transition area between the electrical and acoustical stimulation. Our previous studies demonstrated that bipolar pulses, which are also used during electrical stimulation of the auditory nerve, can certainly damage hair cells and spiral ganglion cells, possibly causing degeneration of the auditory nerve. In the present project, protective stimulation parameters will be defined to minimize the damage physiologically intact areas. Through the use of various neuro- and otoprotective substances, we will attempt to counteract possible adverse effects of electrical stimulation. Protective substances will be studied for their effectiveness alone and in combination with electrical stimulation using various in vitro systems such as dissociated spiral ganglion cell culture or organotypic cultures of the organ of Corti connected to the spiral ganglion. In the latter, auditory hair cells, supporting cells and the afferent and efferent axons and the spiral ganglion neurons in their original 3 -dimensional structure will be examined. Within the complex cochlear structures, individual cell types may react differently, which can only be detected at a single cell-based analysis. Thus, our aim is to perform specific analysis of individual cells, isolated from the cochlea after electrical stimulation. The influence of electrical stimulation alone and in combination with oto- and neuroprotective substances will be studied on cellular (survival and neurite outgrowth), subcellular (activation of intracellular proteins or enzymes that are responsible for protection or apoptosis) and gene expression levels (regulation of pro or anti-apoptotic genes). A particular attention will be paid to the synaptic connections between hair cells and spiral ganglion cells, because of already known synaptic reduction (50 %) described for the inner hair cells as an event proceeding auditory cell loss. Proposed project should generate the ground for the subsequent in vivo project that will then be applied for. In this future project, optimized stimulation parameters and selected protective substances will be used, so that in the future, new approaches can be developed to sustainably preserve the residual hearing in patients supplied with EAS.