Glutamate excitotoxicity on the inner ear and its prorection
| Project/Area Number |
09671747
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 Kiyofumi Ehime University, School of Medicine, Professor, 医学部, 教授 (00108383)
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| Co-Investigator(Kenkyū-buntansha) |
HAKUBA Nobuhiro Ehime University, School of Medicine, Research Assistant, 医学部, 助手 (70304623)
西原 信成 愛媛大学, 医学部・附属病院, 助手 (10274309)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Inner ear ischemia / glutamete / excitotoxicity / inner ear deafness / delayed inner ear damage / electrocochleogram / damage of inner hair cell / primary afferent cochlear nerve / 内耳グルタミン酸 / 遅発性神経障害 / 蝸牛複合電位 |
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| Research Abstract |
L-Glutamate is believed to be a neurotransmitter in the first auditory synapse between the inner hair cell and the dendrite of spiral ganglion type I cell. It is released by a variety of mechanisms, such as anoxia, acoustic trauma and some ototoxic drugs. Although excessive release of glutamate is supposed to work toxic to the surrounding neurons, the exact mechanism in the cochlea remains unclear. In first, we investigated the effects of glutamate on hearing by administration of AMPA, an agonist of glutamate, in the cochlea of guinea pig. AMPA caused a reversible increase in the threshold of cochlear action potential (CAP). Secondly, we studied the glutamate excitotoxicity induced by transient cochlear anoxia by means of occlusion of the bilateral vertebral arteries in gerbil. Five minutes' occlusion caused a drastic increase in CAP threshold, which recovered after recirculation. The threshold returned to preischemic level on the 3rd day, but in some animals it increased again after the : 5th day, suggesting the incidence of delayed neuronal death. Glutamate concentration in the perilymph became higher following ischemic insult. Histological studies revealed the ischemic pathology was severe on the dendrite of the primary afferent auditory nerve constituting synapse with the inner hair cell. Such ischemic damages were prevented by prior administration of glutamate antagonist. These results suggested that excessive glutamate released in the cochlea by anoxia caused damage to the surrounding neurons especially to the dendrite of the primary afferent auditory nerve. Glutamate excitotoxicity is, therefore, supposed to underlie a sensory hearing loss of variety of causes.
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Report
(3 results)
Research Products
(11 results)
