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2003 Fiscal Year Final Research Report Summary

Development of treatment modalities for ischemic cochlear damage

Research Project

Project/Area Number 14370545
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionEhime University

Principal Investigator

GYO Kiyofumi  Ehime University, School of Medicine, Professor, 医学部, 教授 (00108383)

Co-Investigator(Kenkyū-buntansha) SNINOMORI Yusuke  Ehime University, University Hospital, Instructor, 医学部附属病院, 助手 (60335908)
HAKUBA Nobuhiro  Ehime University, School of Medicine, Instructor, 医学部, 助手 (70304623)
HATO Naohito  Ehime University, University Hospital, Lecturer, 医学部附属病院, 講師 (60284410)
Project Period (FY) 2002 – 2003
Keywordsapoptosis / free radical scavenger / ginsenoside Rb1 / glutamate antagonist / GDNF / ischemic hearing loss / excitotoxicity / sudden onset hearing loss
Research Abstract

Prevention of cochlear damage due to inner ear ischemia was investigated based on the underlying apoptotic mechanism. We used Mongolian gerbils as experimental animals, which lack the posterior cerebral communicating arteries and have labyrinthine arteries nourished solely by the vertebral arteries. The animals were subjected to ischemic insult by occluding both vertebral arteries for 15 min. The ischemia caused 20 dB of increase in CAP threshold. Histologically the hair cells and spiral ganglion cells underwent sporadic degeneration, while the damage to the stria vascularis was reversible. The degeneration was proved to be due to apoptosis, which was most prominent at 12 hours of ischemia and was no longer seen later than 3 days.
A variety of treatment modalities were assessed if and how they can prevent ischemia-reperfusion injury of the cochlea. 1.Edarabon (MCI-186) which belongs to a free radical scavenger was proved effective in preventing increase in CAP threshold and degradation of the hair cells, when it was administration intravenously 1 hour after ischemic insult. 2.Lowering of the body temperature to 32 degree (hypothermia) completely blocked degradation of the inner ear, mainly by preventing release of glutamate in the perilymph, reducing production of superoxide and decreasing metabolic rate in the inner ear. 3.Ginsenoside Rb1, which belongs to Kanpo medicine, was also proved effective in prevention of ischemic cochlear damage. 4.AMPA/kainate type of glutamate antagonist such as DNQX was efficient in prevention of cochlear damage, while NMDA type such as D-AP5 had limited value. 5. GDNF which was incorporated in a denatured adenovirus dramatically decreased the cochlear damage due to ischemia, when administered directly into the inner ear.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Taniguchi M, et al.: "Apoptotic hair cell death after transient cochlear ischemia in gerbils."Neuroreport. 13・18. 245-262 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hakuba N, et al.: "Adenovirus-mediated overexpression of a gene prevents hearing loss and progressive inner hair cell in gerbil."Gene Therapy.. 10・5. 426-433 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Koga K, et al.: "Transient cochlear ischemia causes delayed cell death in the organ of Corti : An experimental study in gerbils."J Comp Neurol. 456・2. 105-111 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hakuba N, et al.: "AMPA/kainate-type glutamate receptor antagonist reduces progressive inner hair cell loss after transient cochlear ischemia."Brain Res. 25・979(1-2). 194-202 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maetani T, et al.: "Free radical scavenger protects against inner hair cell loss after cochlear ischemia."Neuroreport. 6・14(14). 1881-1884 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 盛實 勲, 他: "蝸牛神経複合活動電位ならびに蝸牛直流電位に及ぼすグルタミン酸アゴニストの影響"Audiol Jpn. 46. 262-267 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Taniguchi M, et al.: "Apoptotic hair cell death after transient cochlear ischemia in gerbils."Neuroreport. 13・18. 245-262 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hakuba N, et al.: "Adenovirus-mediated overexpression of a gene prevents hearing loss and progressive inner hair cell in gerbil."Gene Therapy. 10・5. 426-433 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] KogaK, et al.: "Transient cochlear ischemia causes delayed cell death in the organ of Corti : An experimental study in gerbils."J Comp Neurol. 456・2. 105-111 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hakuba N, et al.: "AMPA/kainate-type glutamate receptor antagonist reduces progressive inner hair cell loss after transient cochlear ischemia."Brain Res. 25・979(1-2). 194-202 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maetani T, et al.: "Free radical scavenger protects against inner hair cell loss after cochlear ischemia."Neuroreport. 6・14(14). 1881-1884 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Morizane I, et al.: "Effect of glutamate agonist on the compound action potential and the endocochlear DC potential of gerbils"Audiol Jpn. 46・4. 262-267 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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