title: Dexamethasone prevents hearing loss by restoring glucocorticoid receptor expression in the guinea pig cochlea.
abstract: OBJECTIVE
  Dexamethasone is widely used in the treatment of various inner ear diseases. However, knowledge about its direct impact on glucocorticoid receptor (GR) expression is still limited.
  
  
  METHODS
  Prospective animal study in male guinea pigs.
  
  
  METHODS
  A therapeutic concentration of dexamethasone (8 mg/mL) or a physiological concentration of NaCl (0.9% solution) were intratympanically injected into the ears of guinea pigs (n = 10 in each case) 14 hours prior to 90 dB noise exposure (1 hour). Eighteen ears were exposed to noise only. Seven untreated ears were used as controls. Auditory brainstem responses were recorded prior to noise exposure or treatment and 2 hours thereafter. The cochleae were removed from the bullae, transferred to fixative, and embedded in paraffin. GR expression was identified immunohistochemically in the cochlea. Local staining intensities were quantified for seven regions by a computer.
  
  
  RESULTS
  Dexamethasone application significantly lowered noise-induced hearing loss. Statistically significant alterations in the average GR expression levels were identified exclusively in the spiral ligament. Comparing GR expression at the level of individual ear, numerous highly significant local associations were identified in the other six cochlear regions.
  
  
  CONCLUSIONS
  The intratympanic application of dexamethasone is suitable for supporting cochlear homeostasis under stress conditions. The lateral wall, mainly responsible for potassium recycling, seems to be the main target in glucocorticoid therapy.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Ulf-Rüdiger
authors.initials: UR
authors.lastname: Heinrich
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Strieth
authors.affiliation: Institute for Medical Statistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Schmidtmann
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Stauber
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Kai
authors.identifier: http://orcid.org/0000-0002-4502-8731
authors.initials: K
authors.lastname: Helling
mesh_terms: D000818:Animals; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism*; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005938:Glucocorticoids / Q000008:administration & dosage; D006168:Guinea Pigs; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000069555:Injection, Intratympanic; D008297:Male; D011446:Prospective Studies; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis* / Q000187:drug effects
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone
keywords: Glucocorticoids; cochlea; hearing impairment; noise exposure