2019 Fiscal Year Final Research Report
Analysis of Pharmacological Mechanism and effects of the volatile anesthetics Sevoflurane on Neurotransmission in the basal ganglion.
| Project/Area Number |
17K11061
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Anesthesiology
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
宮嶋 雅一 順天堂大学, 医学部, 教授 (60200177)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 吸入麻酔薬 / 線条体 / プレコンディショニング現象 / 過分極活性化型陽イオン電流（Ih電流） / 虚血作用 / 電気生理学 |
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| Outline of Final Research Achievements |
The volatile anesthetic agents, Sevoflurane, has an excellent safety record, but is under review for potential neurotoxicity, especially relevant to administration in infants. And, Volatile anesthetics have been reported to inhibit hyperpolarization activated cyclic-nucleotide gated channels underlying the hyperpolarization-activated cation current (Ih) that contributes to generation of synchronized oscillatory neural rhythms. In our study, the sevoflurane-induced inhibition of Ih in striatal cholinergic interneurons may lead to alterations of the acetylcholine-dopamine balance in the neural circuits during the early postnatal period. As a next step, to investigate the preconditioning effects in the striatum, a common site for ischemic stroke, we collected whole-cell current-clamp recordings from striatal medium spiny neurons. These results indicate that sevoflurane protects striatal neurons from hypoxic damage and alleviates the pathological potentiation.
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| Free Research Field |
麻酔学
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| Academic Significance and Societal Importance of the Research Achievements |
我々麻酔科医が日常的に使用している吸入麻酔薬．幼児期の吸入麻酔薬曝露が学習障害や行動異常を誘発する可能性が指摘され，その作用機序の中心に大脳皮質および海馬、線状体が取りあげられている．その上で近年，加齢に伴う脳機能障害に髄液クリアランスの低下が関与している可能性が示唆されており，これにより脳におけるベータアミロイドなどの有害物質排泄が障害され，認知機能障害の一因になりうると考えられている．多くの脳機能分子が明らかにされつつあるが，今回，主に虚血耐性獲得現象を中心とした研究により麻酔科学研究の中心的課題である麻酔薬の神経回路内伝達制御解明に寄与出来るものと強く考えている．
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