Electrical stimulation of cochlear implant promotes activation of macrophages and fibroblasts under inflammation.

Abstract

The implanted electrodes deliver electric signals to spiral ganglion neurons, conferring restored hearing of cochlear implantation (CI) recipients. Postimplantation intracochlear fibrosis, which is observed in most CI recipients, disturbs the electrical signals and impairs the long-term outcome of CI. The macrophages and fibroblasts activation is critical for the development of intracochlear fibrosis. However, the effect of electric stimulation of cochlear implant (ESCI) on the activity of macrophages and fibroblasts was unclear. In the present study, a human cochlear implant was modified to stimulate cultured macrophages and fibroblasts. By measuring cellular marker and the expression level of cytokine production, the polarization and activity of macrophages and fibroblasts were examined with or without ESCI. Our data showed that ESCI had little effects on the morphology, density, and distribution of culturing macrophages and fibroblasts. Furthermore, ESCI alone did not affect the polarization of macrophages or the function of fibroblasts without the treatment of inflammatory factors. However, in the presence of LPS or IL-4, ESCI further promoted the polarization of macrophages, and increased the expression of pro-inflammatory or anti-inflammatory factors, respectively. For fibroblasts, ESCI further increased the collagen I synthesis induced by TGF-β1 treatment. Nifedipine inhibited ESCI induced calcium influx, and hereby abolished the promoted polarization and activation of macrophages and fibroblasts. Our results suggest that acute inflammation should be well inhibited before the activation of cochlear implants to control the postoperative intracochlear fibrosis. The voltage-gated calcium channels could be considered as the targets for reducing postimplantation inflammation and fibrosis. NA.