Abstract
Aim: To investigate the therapeutic potential for treating inner ear damage of two new steroidal alkaloid compounds, Dendrogenin A and Dendrogenin B, previously shown to be potent inductors of cell differentiation.Methods: Guinea pigs, unilaterally deafened by neomycin infusion, received a cochlear implant followed by immediate or a 2-week delayed treatment with Dendrogenin A, Dendrogenin B, and, as comparison artificial perilymph and glial cell-line derived neurotrophic factor. After a 4-week treatment period the animals were sacrificed and the cochleae processed for morphological analysis. Electrically-evoked auditory brainstem responses (eABRs) were measured weekly throughout the experiment.Results: Following immediate or delayed Dendrogenin treatment the electrical responsiveness was significantly maintained, in a similar extent as has been shown using neurotrophic factors. Histological analysis showed that the spiral ganglion neurons density was only slightly higher than the untreated group.Conclusions: Our results suggest that Dendrogenins constitute a new class of drugs with strong potential to improve cochlear implant efficacy and to treat neuropathy/synaptopathy related hearing loss. That electrical responsiveness was maintained despite a significantly reduced neural population suggests that the efficacy of cochlear implants is more related to the functional state of the spiral ganglion neurons than merely their number.
Highlights
The biological properties of two new alkylaminooxysterols have been characterized by de Medina et al (2009)
The results have suggested that cochlear implant efficacy is closely related to the number of remaining spiral ganglion neurons
Electrical Responsiveness of the Spiral Ganglion In the model used in the present study, the animals are chemically deafened in order to mimic different stages of human deafness
Summary
The biological properties of two new alkylaminooxysterols have been characterized by de Medina et al (2009). One of the most common sensory deficits, hearing impairment, involves a progressive degeneration of structures within the inner ear, including the auditory nerve fibers and subsequently the spiral ganglion neurons themselves. Damage to the hair cells results in hearing impairment that, can be functionally compensated for by implanting a cochlear prosthesis providing electrical stimulation of the nerve fibers, bypassing the dysfunctional sensory cells. The progressive peripheral nerve fiber regression and subsequent degeneration of the cells in the spiral ganglion can diminish its efficacy (Maruyama et al, 2008; Fransson et al, 2010). Drugs that maintain the structural and functional integrity of the auditory neurons are likely to further improve the benefits of cochlear implant for hearing impaired patients
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