AUTHOR=Fransson Anette , de Medina Philippe , Paillasse Michaël R. , Silvente-Poirot Sandrine , Poirot Marc , Ulfendahl Mats 

TITLE=Dendrogenin A and B two new steroidal alkaloids increasing neural responsiveness in the deafened guinea pig

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=7

YEAR=2015

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2015.00145

DOI=10.3389/fnagi.2015.00145

ISSN=1663-4365

ABSTRACT=<p><bold>Aim:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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.</p><p><bold>Conclusions:</bold> 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.</p>