Neuronal Survival, Morphology and Outgrowth of Spiral Ganglion Neurons Using a Defined Growth Factor Combination

PLoS One. 2015 Aug 11;10(8):e0133680. doi: 10.1371/journal.pone.0133680. eCollection 2015.

Abstract

Objectives: The functionality of cochlear implants (CI) depends, among others, on the number and excitability of surviving spiral ganglion neurons (SGN). The spatial separation between the SGN, located in the bony axis of the inner ear, and the CI, which is inserted in the scala tympani, results in suboptimal performance of CI patients and may be decreased by attracting the SGN neurites towards the electrode contacts. Neurotrophic factors (NTFs) can support neuronal survival and neurite outgrowth.

Methods: Since brain-derived neurotrophic factor (BDNF) is well known for its neuroprotective effect and ciliary neurotrophic factor (CNTF) increases neurite outgrowth, we evaluated if the combination of BDNF and CNTF leads to an enhanced neuronal survival with extended neurite outgrowth. Both NTFs were added in effective high concentrations (BDNF 50 ng/ml, CNTF 100 ng/ml), alone and in combination, to cultured dissociated SGN of neonatal rats for 48 hours.

Results: The neuronal survival and neurite outgrowth were significantly higher in SGN treated with the combination of the two NTFs compared to treatment with each factor alone. Additionally, with respect to the morphology, the combination of BDNF and CNTF leads to a significantly higher number of bipolar neurons and a decreased number of neurons without neurites in culture.

Conclusion: The combination of BDNF and CNTF shows a great potential to increase the neuronal survival and the number of bipolar neurons in vitro and to regenerate retracted nerve fibers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Female
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Male
  • Neurites / drug effects
  • Neurites / metabolism
  • Neurons / cytology*
  • Neurons / drug effects*
  • Rats
  • Spiral Ganglion / cytology*

Substances

  • Intercellular Signaling Peptides and Proteins

Grants and funding

The work was supported by the DFG (German Research Foundation, “Deutsche Forschungsgemeinschaft”) SFB599 project D2 (http://www.sfb599.de/) (JS) and the cluster of excellence “Hearing4all” (http://hearing4all.eu/EN/) (AW), and by the EC project (project number: 304930) NeuEar: Neurotrophic Cochlea Implant for Severe Hearing Loss (http://www.neuear.eu/) (VS, JS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.