Mechanisms of programmed cell death signaling in hair cells and support cells post-electrode insertion trauma

Adrien Eshraghi, Dustin M. Lang, Jonathan Roell, Thomas R Van De Water, Carolyn Garnham, Helio Rodrigues, Mateo Guardiola, Chhavi Gupta, Jeenu Mittal

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Conclusion: Programmed cell death (PCD) initially starts in the support cells (SCs) after electrode insertion trauma (EIT), followed by PCD in hair cells (HCs). Activation of caspase-3 was observed only in SCs. Protecting both SCs and HCs with selective otoprotective drugs at an early stage post implantation may help to preserve residual hearing. Objectives: Cochlear implant EIT can initiate sensory cell losses via necrosis and PCD within the organ of Corti, which can lead to a loss of residual hearing. PCD appears to be a major factor in HC loss post-EIT. The current study aimed to: (1) determine the onset of PCD in both SCs and HCs within the traumatized organ of Corti; and (2) identify the molecular mechanisms active within the HCs and SCs that are undergoing PCD. Methods: Adult guinea pigs were assigned to one of two groups: (1) EIT and (2) unoperated contralateral ears as controls. Immunostaining of dissected organ of Corti surface preparations for phosphorylated-Jun, cleaved caspase-3, and 4-hydroxy-2,3-nonenal (HNE) were performed at 6, 12, and 24 h post-EIT and for contralateral control ears. Results: At 6 h post-EIT the SCs immunolabeled for the presence of phosphorylated-Jun and activated caspase-3. Phosphorylated p-Jun labeling was observed at 12 h in both the HCs and SCs of middle and basal cochlear turns. Cleaved caspase-3 was not observed in HCs of any cochlear turn at up to 24 h post-EIT. Lipid peroxidation (HNE immunostaining) was first observed at 12 h post-EIT in both the HCs and SCs of the basal turn, and reached the apical turn by 24 h post-EIT.

Original languageEnglish (US)
Pages (from-to)328-334
Number of pages7
JournalActa Oto-Laryngologica
Volume135
Issue number4
DOIs
StatePublished - Apr 1 2015

Keywords

  • Cochlear implant
  • Electrode insertion trauma grading system
  • Electrode-induced trauma
  • Hair cell loss

ASJC Scopus subject areas

  • Otorhinolaryngology

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    Eshraghi, A., Lang, D. M., Roell, J., Van De Water, T. R., Garnham, C., Rodrigues, H., Guardiola, M., Gupta, C., & Mittal, J. (2015). Mechanisms of programmed cell death signaling in hair cells and support cells post-electrode insertion trauma. Acta Oto-Laryngologica, 135(4), 328-334. https://doi.org/10.3109/00016489.2015.1012276