Closing the Gap between the Auditory Nerve and Cochlear Implant Electrodes: Which Neurotrophin Cocktail Performs Best for Axonal Outgrowth and Is Electrical Stimulation Beneficial?

Abstract

Neurotrophins promote neurite outgrowth of auditory neurons and may help closing the gap to cochlear implant (CI) electrodes to enhance electrical hearing. The best concentrations and mix of neurotrophins for this nerve regrowth are unknown. Whether electrical stimulation (ES) during outgrowth is beneficial or may direct axons is another open question. Auditory neuron explant cultures of distinct cochlear turns of 6–7 days old mice were cultured for four days. We tested different concentrations and combinations of BDNF and NT-3 and quantified the numbers and lengths of neurites with an advanced automated analysis. A custom-made 24-well electrical stimulator based on two bulk CIs served to test different ES strategies. Quantification of receptors trkB, trkC, p75NTR, and histological analysis helped to analyze effects. We found 25 ng/mL BDNF to perform best, especially in basal neurons, a negative influence of NT-3 in combined BDNF/NT-3 scenarios, and tonotopic changes in trk and p75NTR receptor stainings. ES largely impeded neurite outgrowth and glia ensheathment in an amplitude-dependent way. Apical neurons showed slight benefits in neurite numbers and length with ES at 10 and 500 µA. We recommend BDNF as a potent drug to enhance the man-machine interface, but CIs should be better activated after nerve regrowth.

The effects of mild hypothermia on the electrode insertion trauma in a murine whole organ cochlea culture

“…Obtaining an informative result from the whole organ cochlea culture model depends on the number of surviving cells. The application of neurotrophic factors as described above to neuronal cultures—like the used whole organ cochlea culture—has been shown to promote cell survival ( Schmidbauer et al, 2023 ). Therefore, the influence of these factors on the reported results need to be discussed.…”

Emerging biotechnologies and biomedical engineering technologies for hearing reconstruction

“…[61][62][63][64] The latter is induced by fibrosis in the cochlea and new ear bones so that the host's response time to the electrical signal is prolonged. 61,65 Therefore, researchers have focused on the CI electrode surface coating prepared by different biomaterials to deliver neurotrophins, [66][67][68] genes, 69 or cells [70][71][72] to improve the microenvironment after implantation and hearing.…”