title: Effects of Intratympanic Dexamethasone on High-Dose Radiation Ototoxicity In Vivo.
abstract: Stereotactic radiosurgery for lateral skull base tumors can cause hearing loss when the cochleae are exposed to high doses of single-fraction radiation. Currently, there are no known nondosimetric preventative treatments for radiation-induced ototoxicity.
  
  
  
  Intratympanic (IT) dexamethasone (DXM), a synthetic steroid, protects against radiation-induced auditory hair cell (HC) and hearing losses in rats in vivo.
  
  
  
  Seven rats received radiation (12 Gy) to both cochleae. In irradiated rats and six nonirradiated rats, IT DXM was randomized to one ear, while tympanic puncture without DXM was performed on the contralateral ear. Baseline and 4-week postradiation auditory-evoked potential tests were performed. The cochleae were processed for HC viability.
  
  
  
  Cochleae exposed to radiation demonstrated more outer HC (OHC) loss in all turns than nonirradiated ears (p <0.05). OHCs were more susceptible to radiation injury than inner HCs in the middle and basal turns (p <0.05). In irradiated cochleae, there was a nonsignificant trend for less OHC loss with IT DXM in the basal turn when compared with placebo. IT DXM did not improve radiation-induced hearing threshold shifts; however, a high rate of tympanic membrane perforations occurred with irradiated ears which may contribute to this finding.
  
  
  
  Radiation induced loss of OHCs in all turns of the cochlea. IT DXM reduced OHC loss in the basal turn of irradiated ears; however, this finding did not achieve statistical significance. Although IT DXM did not affect radiation-induced hearing threshold shifts in adult rats in vivo, this may be due to a high rate of tympanic membrane perforations.
authors.affiliation: *Department of Otolaryngology-Head and Neck Surgery †Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Christine T
authors.initials: CT
authors.lastname: Dinh
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Dinh
authors.forename: Stefania
authors.initials: S
authors.lastname: Goncalves
authors.forename: Esperanza
authors.initials: E
authors.lastname: Bas
authors.forename: Kyle
authors.initials: K
authors.lastname: Padgett
authors.forename: Perry
authors.initials: P
authors.lastname: Johnson
authors.forename: Nagy
authors.initials: N
authors.lastname: Elsayyad
authors.forename: Fred
authors.initials: F
authors.lastname: Telischi
authors.forename: Thomas
authors.initials: T
authors.lastname: Van De Water
mesh_terms: D000818:Animals; D003051:Cochlea / Q000187:drug effects* / Q000528:radiation effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D005072:Evoked Potentials, Auditory / Q000187:drug effects* / Q000528:radiation effects; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000528:radiation effects; D034381:Hearing Loss / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D011827:Radiation; D051381:Rats; D014432:Tympanic Membrane / Q000187:drug effects* / Q000528:radiation effects
chemical_list: D003907:Dexamethasone