title: Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils.
abstract: OBJECTIVE
  Auditory neuropathy (AN) is a hearing disorder characterized by abnormal auditory nerve function with preservation of normal cochlear hair cells. This study was designed to investigate whether treatment with molecular hydrogen (H(2)), which can remedy damage in various organs via reducing oxidative stress, inflammation and apoptosis, is beneficial to ouabain-induced AN in gerbils.
  
  
  METHODS
  AN model was made by local application of ouabain (1 mmol/L, 20 mL) to the round window membrane in male Mongolian gerbils. H(2) treatment was given twice by exposing the animals to H(2) (1%, 2%, and 4%) for 60 min at 1 h and 6 h after ouabain application. Before and 7 d after ouabain application, the hearing status of the animals was evaluated using the auditory brainstem response (ABR) approach, the hear cell function was evaluated with distortion product otoacoustic emissions (DPOAE). Seven days after ouabain application, the changes in the cochleae, especially the spiral ganglion neurons (SGNs), were morphologically studied. TUNEL staining and immunofluorescent staining for activated caspase-3 were used to assess the apoptosis of SGNs.
  
  
  RESULTS
  Treatment with H(2) (2% and 4%) markedly attenuated the click and tone burst-evoked ABR threshold shift at 4, 8, and 16 kHz in ouabain-exposed animals. Neither local ouabain application, nor H(2) treatment changed the amplitude of DPOAE at 4, 8, and 16 kHz. Morphological study showed that treatment with H(2) (2%) significantly alleviated SGN damage and attenuated the loss of SGN density for each turn of cochlea in ouabain-exposed animals. Furthermore, ouabain caused significantly higher numbers of apoptotic SGNs in the cochlea, which was significantly attenuated by the H(2) treatment. However, ouabain did not change the morphology of cochlear hair cells.
  
  
  CONCLUSIONS
  The results demonstrate that H(2) treatment is beneficial to ouabain-induced AN via reducing apoptosis. Thus, H(2) might be a potential agent for treating hearing impairment in AN patients.
authors.affiliation: Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Qu
authors.forename: Yun-na
authors.initials: YN
authors.lastname: Gan
authors.forename: Ke-liang
authors.initials: KL
authors.lastname: Xie
authors.forename: Wen-bo
authors.initials: WB
authors.lastname: Liu
authors.forename: Ya-fei
authors.initials: YF
authors.lastname: Wang
authors.forename: Ren-yi
authors.initials: RY
authors.lastname: Hei
authors.forename: Wen-juan
authors.initials: WJ
authors.lastname: Mi
authors.forename: Jian-hua
authors.initials: JH
authors.lastname: Qiu
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D003051:Cochlea / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D005740:Gases / Q000008:administration & dosage / Q000627:therapeutic use; D005849:Gerbillinae; D006309:Hearing / Q000187:drug effects; D006313:Hearing Loss, Central / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D006859:Hydrogen / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010042:Ouabain / Q000009:adverse effects*
chemical_list: D005740:Gases; D010042:Ouabain; D006859:Hydrogen; D053148:Caspase 3