title: Changes in Gene Expression and Hearing Thresholds After Cochlear Implantation.
abstract: OBJECTIVE
  Gene expression changes occur in conjunction with hearing threshold changes after cochlear implantation.
  
  
  BACKGROUND
  Between 30 and 50% of individuals who receive electro-acoustic stimulation (EAS) cochlear implants lose residual hearing after cochlear implantation, reducing the benefits of EAS. The mechanism underlying this hearing loss is unknown; potential pathways include mechanical damage, inflammation, or tissue remodeling changes.
  
  
  METHODS
  Guinea pigs were implanted in one ear with cochlear implant electrode arrays, with non-implanted ears serving as controls, and allowed to recover for 1, 3, 7, or 14 days. Hearing threshold changes were measured over time. Cochlear ribonucleic acid was analyzed using real-time quantitative reverse transcription-polymerase chain reaction from the following gene families: cytokines, tight junction claudins, ion and water (aquaporin) transport channels, gap junction connexins, and tissue remodeling genes.
  
  
  RESULTS
  Significant increases in expression were observed for cochlear inflammatory genes (Cxcl1, IL-1β, TNF-α, and Tnfrsf1a/b) and ion homeostasis genes (Scnn1γ, Aqp3, and Gjb3). Upregulation of tissue remodeling genes (TGF-β, MMP2, MMP9) as well as a paracrine gene (CTGF) was also observed. Hearing loss occurred rapidly, peaking at 3 days with some recovery at 7 and 14 days after implantation. MM9 exhibited extreme upregulation of expression and was qualitatively associated with changes in hearing thresholds.
  
  
  CONCLUSIONS
  Cochlear implantation induces similar changes as middle ear inflammation for genes involved in inflammation and ion and water transport function, whereas tissue remodeling changes differ markedly. The upregulation of MMP9 with hearing loss is consistent with previous findings linking stria vascularis vessel changes with cochlear implant-induced hearing loss.
authors.affiliation: *Department of Otolaryngology Head & Neck Surgery, Zhujiang Hospital of Southern Medical University, Guangzhou, China; and †Oregon Hearing Research Center, Department of Otolaryngology, Oregon Health and Science University, Portland, Oregon, U.S.A.
authors.forename: Hongzheng
authors.initials: H
authors.lastname: Zhang
authors.forename: Gemaine
authors.initials: G
authors.lastname: Stark
authors.forename: Lina
authors.initials: L
authors.lastname: Reiss
mesh_terms: D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D019929:Cochlear Implantation / Q000009:adverse effects*; D003054:Cochlear Implants; D004195:Disease Models, Animal; D006168:Guinea Pigs; D034381:Hearing Loss / Q000601:surgery; D007249:Inflammation / Q000209:etiology* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000502:physiology*
chemical_list: D020780:Matrix Metalloproteinase 9