Over-expression of BDNF by adenovirus with concurrent electrical stimulation improves cochlear implant thresholds and survival of auditory neurons

Hear Res. 2008 Nov;245(1-2):24-34. doi: 10.1016/j.heares.2008.08.005. Epub 2008 Aug 19.


The survival of the auditory nerve in cases of sensorineural hearing loss is believed to be a major factor in effective cochlear implant function. The current study assesses two measures of cochlear implant thresholds following a post-deafening treatment intended to halt auditory nerve degeneration. We used an adenoviral construct containing a gene insert for brain-derived neurotrophic factor (BDNF), a construct that has previously been shown to promote neuronal survival in a number of biological systems. We implanted ototoxically deafened guinea pigs with a multichannel cochlear implant and delivered a single inoculation of an adenovirus suspension coding for BDNF (Ad.BDNF) into the scala tympani at the time of implantation. Thresholds to electrical stimulation were assessed both psychophysically and electrophysiologically over a period of 80 days. Spiral ganglion cell survival was analyzed at the 80 days time point. Compared to the control group, the Ad.BDNF treated group had lower psychophysical and electrophysiological thresholds as well as higher survival of spiral ganglion cells. Electrophysiological, but not psychophysical, thresholds correlated well with the density of spiral ganglion cells. These results indicate that the changes in the anatomy of the auditory nerve induced by the combination of Ad.BDNF inoculation and the electrical stimulation used for testing improved functional measures of CI performance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Auditory Threshold / physiology*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Brain-Derived Neurotrophic Factor / physiology*
  • Cell Survival
  • Cochlear Implants*
  • Cochlear Nerve / cytology
  • Cochlear Nerve / physiology*
  • Electric Stimulation Therapy
  • Electrophysiology
  • Evoked Potentials, Auditory, Brain Stem
  • Gene Expression
  • Genetic Vectors
  • Guinea Pigs
  • Hearing Loss, Sensorineural / physiopathology
  • Hearing Loss, Sensorineural / therapy
  • Humans
  • Male
  • Psychoacoustics
  • Recombinant Proteins / genetics


  • Brain-Derived Neurotrophic Factor
  • Recombinant Proteins