Abstract
ObjectivesThe 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.MethodsSince 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 50ng/ml, CNTF 100ng/ml), alone and in combination, to cultured dissociated SGN of neonatal rats for 48 hours.ResultsThe 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.ConclusionThe 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.
Highlights
Cochlear implants (CI) are the standard therapy for patients suffering from sensory neural hearing loss
The neuronal survival and neurite outgrowth were significantly higher in spiral ganglion neurons (SGN) treated with the combination of the two neurotrophic factors (NTFs) compared to treatment with each factor alone
Neuronal survival can be increased by electrical stimulation [2,3,4,5,6,7] or neurotrophic factors (NTFs)
Summary
Cochlear implants (CI) are the standard therapy for patients suffering from sensory neural hearing loss. The most important aspects, which hinder further improvement of CI outcome, are the retraction of the peripheral nerve fibers of the spiral ganglion neurons (SGN) following hair cell loss and the degeneration of the SGN in patients with long-time deafness. As previously summarized [8], the intracellular signaling pathways for BDNF are well examined It acts by the activation of the tyrosine receptor kinase B (trkB) receptor ( named neurotrophic tyrosine kinase receptor type 2 (NTRK2)), which is present in different cell-types of the spiral ganglion [9]. Various downstream pathways promoting cell survival are activated when BDNF binds to the trkB receptors. Different co-factors in the divers signaling pathways that result in the activation of CREB are important determinants of the CREB-dependent gene targeting [12]. A synergy between the neurotrophin family members and other NTFs may influence the recruitment of such co-factors
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