| Project/Area Number |
16591556
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Nara Medical University |
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Principal Investigator |
INOUE Satoki Nara Medical University, 医学部, Assistant Prof (50295789)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAGUCHI Masahiko Nara Medical University, 医学部, Associated Prof (60275328)
SASAOKA Noriyuki Nara Medical University, 医学部, Staff (70364073)
FURUYA Hitoshi Nara Medical University, 医学部, Professor (70183598)
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| Project Period (FY) |
2004 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥2,910,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Neuroprotection / Delta opioid / Cerebral ischemia / Brain protection |
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| Research Abstract |
BACKGROUND: It has been reported that delta-opioid (DOP) receptor agonists may be neuroprotective in the central nervous system. However, the DOP agonist [d-Ala (2), d-Leu (5)] enkephalin (DADLE) does not produce neuroprotection in severe forebrain ischemia. The aim of this study was to examine the effects of DADLE on hippocampal neurone survival against less severe forebrain ischemia. METHODS: Intraperitoneal injection of DADLE (0 or 16 mg kg (-1)) in male Sprague-Dawley rats was performed 30 min before ischemia. Severe (10 min), moderate (8 min), or mild (6 min) forebrain ischemia was produced by bilateral carotid occlusion combined with hypotension (35 mm Hg) under isoflurane (1.5%) anesthesia. Naltrindole (10 mg kg (-1)) (DOP antagonist) was administered 30 min before DADLE in order to confirm DOP receptor activation in the neuroprotective efficacy of DADLE. Naltrindole alone was also administered 30 min before ischemia to examine endogenous DOP agonism as a self-protecting mechani
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sm against ischemia. All animals were evaluated neurologically and histologically after a1 week recovery period. RESULTS: DADLE improved neurone survival in hippocampal CA3 and dentate gyrus (DG) sectors. CA1 neurones were not protected against moderate and mild ischemia. Naltrindole abolished DADLE neuroprotection in the CA3 and DG after both moderate and mild ischemia. Interestingly, regardless of co-administration of DADLE, naltrindole significantly worsened neuronal injury in the CA1 region after mild ischemia. CONCLUSIONS: These results suggest that DADLE provides limited neuroprotection to relatively ischemia-resistant regions but not to selectively vulnerable regions. This was probably mediated by DOP stimulation. Pre-ischaemic treatment with a DOP antagonist, regardless of co-administration of DADLE, worsened neuronal damage at the selectively vulnerable regions only after mild forebrain ischemia. These data suggest that DOP activation with endogenous DOP ligand may be involved in self-protecting ischemia-sensitive regions of the brain. Less
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