title: Protection against ischemic cochlear damage by intratympanic administration of AM-111.
abstract: OBJECTIVE
  AM-111, a cell-permeable peptide inhibitor of c-Jun N-terminal kinase, was investigated for its protective effects against ischemic damage of the cochlea in gerbils.
  
  
  METHODS
  Transient cochlear ischemia was introduced in animals by occluding the bilateral vertebral arteries for l5 minutes. Then, 10 μl of AM-111 at a concentration of l, 10, or 100 μM in hyaluronic acid gel formulation was applied onto the round window 30 minutes after the insult. Gel without active substance was used in a control group. Treatment effects were evaluated by auditory brainstem response (ABR) and histology of the inner ear.
  
  
  RESULTS
  In controls, transient cochlear ischemia caused a 25.0 ± 5.0 dB increase in the ABR threshold at 8 kHz and a decrease of 13.3 ± 2.3% in inner hair cells at the basal turn on Day 7. Ischemic damage was mild at 2 and 4 kHz. When the animals were treated with AM-111 at 100 μM, cochlear damage was significantly reduced: the increase in ABR threshold was 3.3 ± 2.4 dB at 8 kHz, and the inner hair cell loss was 3.1 ± 0.6% at the basal turn on Day 7. The effects of AM-111 were concentration dependent: 100 μM was more effective than 1 or 10 μM.
  
  
  CONCLUSIONS
  Direct application of AM-111 in gel formulation on the round window was effective in preventing acute hearing loss because of transient cochlear ischemia.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Ehime University, Ehime, Japan. omotehar@m.ehime-u.ac.jp
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Omotehara
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Hakuba
authors.forename: Naohito
authors.initials: N
authors.lastname: Hato
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okada
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Gyo
mesh_terms: D000818:Animals; D003051:Cochlea / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005849:Gerbillinae; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology; D034381:Hearing Loss / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007511:Ischemia / Q000150:complications* / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D010455:Peptides; C478085:D-JNKI-1