| Project/Area Number |
09307039
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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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 | University of Tsukuba, Institute of Clinical Medicine |
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Principal Investigator |
KUSAKARI Jun Institute of Clinical Medicine, Department of Otolaryngology, Professor., 臨床医学系, 教授 (00004705)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Tetsuro Institute of Clinical Medicine, Department of Otolaryngology, Assistant Professor., 臨床医学系, 講師 (10282360)
ITO Zenya Institute of Clinical Medicine, Department of Otolaryngology, Assistant Professor., 臨床医学系, 講師 (20241812)
HARA Akira Institute of Clinical Medicine, Department of Otolaryngology, Associate Professor., 臨床医学系, 助教授 (10156474)
SENARITA Masamitsu Institute of Clinical Medicine, Department of Otolaryngology, Assistant Professor., 臨床医学系, 講師 (60282357)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥19,400,000 (Direct Cost: ¥19,400,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1997: ¥14,000,000 (Direct Cost: ¥14,000,000)
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| Keywords | Cochlea / Transient Ischemia / Ischemia-reperfusion Injury / Free Radicals / NO / iNOS / nNOS / OH / 蝸牛一過性虚血 / 蝸牛一過性アノキシア / 蝸牛神経活動電位 / PARS / Phospholipase A2 / カルモデュリン / ステロイドホルモン / 蝸牛神経複合活動電位 / NOS阻害剤 / NMDA受容体拮抗剤 / PARS抑制剤 / A1アデノシン受容体作動薬 / Mn-SOD / マンニットール / 鉄イオン |
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| Research Abstract |
In order to examine the role of free radicals in the generation mechanism of ischemia-reperfusion injury in the cochlea, transient ischemia was induced in the guinea pigs by pressing the labyrinthine artery at the porus acousticus internus. Ischemia of 15 minutes or longer induced the significant threshold shift of the compound action potential at 4 hours after the restoration of the blood flow, whereas the observation at 5 days after the exposure to transient ischemia indicated that the permanent threshold shift of auditory brainstem response was induced by ischemia of 30 minutes or longer. At the post ischemic period, an increase of OH and iron in perilymph was biochemically confirmed and physiological studies strongly suggested an increased production of NO.Electrophysiological and morphological, in part, studies clearly showed that various substances inhibiting the responses to produce OH as well as NO (and ONOO) exerted the protective effect upon the reperfusion injury. The conclusion of the present studies is as follows.
(1) Excitotoxicity probably due to glutamate is likely to exsert its noxious effect only during the period of ischemia but not the period of reperfusion.
(2) OH as well as NO (and ONOO) increases during the reperfusion period and plays ant important role in the generation mechanism of the cochlear injury.
(3) NO is induced by nNoS and iNoS at the early stage and the later stage of the reperfusion period, respectively.
(4) Although main injury sites are the outer hair cells, the inner hair cells and the cochlear neuron during ischemia, the outer hair cells are mainly involved during the period of reperfusion injury.
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