title: Mechanisms of programmed cell death signaling in hair cells and support cells post-electrode insertion trauma.
abstract: CONCLUSIONS
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: University of Miami Miller School of Medicine , Miami, FL , USA.
authors.forename: Adrien A
authors.initials: AA
authors.lastname: Eshraghi
authors.forename: Dustin M
authors.initials: DM
authors.lastname: Lang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Roell
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Van De Water
authors.forename: Carolyn
authors.initials: C
authors.lastname: Garnham
authors.forename: Helio
authors.initials: H
authors.lastname: Rodrigues
authors.forename: Mateo
authors.initials: M
authors.lastname: Guardiola
authors.forename: Chhavi
authors.initials: C
authors.lastname: Gupta
authors.forename: Jeenu
authors.initials: J
authors.lastname: Mittal
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D019929:Cochlear Implantation / Q000009:adverse effects* / Q000295:instrumentation; D003054:Cochlear Implants / Q000009:adverse effects*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000378:metabolism / Q000473:pathology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007760:Labyrinth Supporting Cells / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors
chemical_list: D000447:Aldehydes; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; C027576:4-hydroxy-2-nonenal
keywords: cochlear implant; electrode insertion trauma grading system; electrode-induced trauma; hair cell loss