| Project/Area Number |
18390459
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Ehime University |
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Principal Investigator |
GYO Kiyofiuni Ehime University, Graduate School of Medicine, Professor (00108383)
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| Co-Investigator(Kenkyū-buntansha) |
HATA Ryuji Ehime University, Graduate School of Medicine, Associate Professor (90258153)
HATO Naohito Ehime University, University Hospital, Senior Assistant Profesthr (60284410)
HYODO Jun Ehime University, University Hospital, Senior Assistant Professor (30423453)
TAKEDA Shoichiro Ehime University, University Hospital, Senior Intern (70403821)
篠森 裕介 愛媛大学, 医学部附属病院, 講師 (60335908)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥14,250,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2007: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2006: ¥11,000,000 (Direct Cost: ¥11,000,000)
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| Keywords | transient cochlear ischemia / post-ischemic process / glutamate antagonist / free daical scavenger / predonisone / apoptosis / AM-111 / sudden sensorineural deafness / 一過性虚血 / 治療の窓 / プロサポシン由来合成ペプチド / ゼラチンハイドロゲル / インシュリン様細胞増殖因子 / 内耳低温療法 / エダラボン / ジンセノサイド / 神経幹細胞 / GDNF |
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| Research Abstract |
Cochlear ischemia is supposed to be one of the major causes of idiopathic sudden sensorineural hearing loss (ISSH). The present study was conducted to reveal the mechanisms of cochlear damage in an animal model of transient cochlear ischemia using Mongolian gerbils. We further evaluated various therapeutic agents to develop a new treatment modality based on the therapeutic time window. Loading of transient cochlear ischemia for I5-min demonstrated that the cochlea was damaged not only by energy failure but also by a large amount of free radicals induced in the inner ear. Excessive release of glutamate from the synaptic clefts exclusively devastated the inner hair cells and the spiral ganglion neurons. Post-ischemic processes differed by the sites of the cochlea. Damage of the stria vascularis was severe immediate after the ischemia, which recovered gradually within a week. In the organ of Corti, the hair cells underwent apoptotic cell death that went on for 3 days. Degeneration of the spiral ganglion neurons progressed slowly, which lasted for more than a week. They were supposed to be due to secondary degeneration following death of the inner hair cells.
In the treatment of ischemic cochlear damage, recovery of the blood supply is essential. Application of glutamate antagonist is effective only when applied immediate after the insult. This seems clinically impractical. In contrast, application of free radical scavenger (edaravon) or predonisone was effective to prevent damages of the cochlea. Furthermore, AM-111, a blocker of apoptotic process, protected death of the inner hair cells. All these findings suggested that treatment of ISSH should be individualized base on the therapeutic time window, since degenerative processes of the cochlea sequentially change after the onset of ischemia.
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