title: Dendrogenin A and B two new steroidal alkaloids increasing neural responsiveness in the deafened guinea pig.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neuroscience, Karolinska Institutet Stockholm, Sweden.
authors.forename: Anette
authors.initials: A
authors.lastname: Fransson
authors.affiliation: Affichem SA Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: de Medina
authors.affiliation: Affichem SA Toulouse, France.
authors.forename: Michaël R
authors.initials: MR
authors.lastname: Paillasse
authors.affiliation: INSERM UMR 1037, Cancer Research Center of Toulouse Toulouse, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Silvente-Poirot
authors.affiliation: INSERM UMR 1037, Cancer Research Center of Toulouse Toulouse, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Poirot
authors.affiliation: Department of Neuroscience, Karolinska Institutet Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Ulfendahl
keywords: auditory nerve; cochlear implant; electrically-evoked auditory brainstem response; spiral ganglion neuron; steroidal alkaloid