2014 Fiscal Year Annual Research Report
グリアの動態変化に及ぼす全身麻酔薬の作用～麻酔メカニズムの統一化に向けて～
| Project/Area Number |
24249077
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| Research Institution | Osaka University |
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Principal Investigator |
真下 節 大阪大学, その他部局等, 名誉教授 (10110785)
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| Co-Investigator(Kenkyū-buntansha) |
吉岡 芳親 大阪大学, 免疫学フロンティア研究センター, 教授 (00174897)
下瀬川 恵久 大阪大学, 医学(系)研究科(研究院), 教授 (30370258)
島岡 要 三重大学, 医学(系)研究科(研究院), 教授 (40281133)
中江 文 大阪大学, 免疫学フロンティア研究センター, 准教授 (60379170)
畑澤 順 大阪大学, 医学(系)研究科(研究院), 教授 (70198745)
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| Project Period (FY) |
2012-04-01 – 2017-03-31
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| Keywords | 麻酔メカニズム / PET |
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| Outline of Annual Research Achievements |
本研究は「麻酔は何故効くか」について、すべての麻酔薬に共通する作用メカニズムを解明するために、この研究領域ではこれまで着目されてこなかったグリア細胞に焦点を当てて、マクロとミクロのレベルでの麻酔薬の作用を明らかにすることを目的とする。
そのために、グリア細胞の機能低下をどのように示すかの検討を詳細に行い、まず、AcetatePETの解析を進めた。その結果、アセテートの洗い出し曲線を用いた解析において、比較的浅い麻酔であるセボフルレン1.5%と深麻酔である4.0％セボフルレンの間に有意なグリア細胞の機能低下を認めた（ｐ＜０．０５）。さらに、FDG－PETにおいても同様にグルコース代謝の低下を認め、従来の知見、人における知見との一致をみた。さらに、部位ごとの解析を進めていくにあたり、検討した結果、現在の個体数では有意な変化を得られにくいとの結論に達し、さらに8週令のSDラットを用いて、各群5匹ずつAcetatePETの撮像を行った。撮像が3月半ばまでかかったため、解析はこれから進める予定である。
さらに、MRIにおける機能的脳結合の解析についての検討を行った。動物で高解像MRIで機能的な脳結合を明らかにすることは非常に困難であるが、そのネットワーク形態変化を明らかにすることを目標とすると同時に、特定部位を中心とした解析方法の可能性の検討を行い、撮像方法論の候補を挙げることが出来た。次年度の実際の撮像に向けて詳細の検討を終了することが出来た。
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
本年度Acetate－PETの結果の解析により、麻酔深度が深くなるにつれてグリア細胞の機能が低下していることが明らかとなり、全脳レベルでのグリア細胞の機能低下という、第一段階の証拠をつかむことが出来たため。
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| Strategy for Future Research Activity |
本年度取得したデータを加えて、脳を標準画像に変換し、各部位ごとのグリア細胞の機能変化を明らかにする。さらに、本年度はMRIで機能的ネットワークの変化を同定できる実験系を立ち上げ、特にグリア細胞の活動の低下した部位と他の重要な領域の機能的ネットワークの変化を明らかにすることを目指していく。
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[Journal Article] Olfactory Plays a Key Role in Spatiotemporal Pathogenesis of Cerebral Malaria.2014
Author(s)
Zhao H, Aoshi T, Kawai S, Mori Y, Konishi A, Ozkan M, Fujita Y, Haseda Y, Shimizu M, Kohyama M, Kobiyama K, Eto K, Nabekura J, Horii T, Ishino T,, Kinoshita M, Tohyama K, Yoshioka Y, Ishii KJ, Coban C
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Journal Title
Cell Host & Microbe
Volume: 15
Pages: 551-563
DOI
Peer Reviewed
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[Journal Article] A new mouse allele of glutamate receptor delta 2 with cerebellar atrophy and progressive ataxia.2014
Author(s)
Miyoshi Y, Yoshioka Y, Suzuki K, Miyazaki T, Koura M, Saigoh K, Kajimura N, Monobe Y, Kusunoki S, Matsuda J, Watanabe M, Hayasaka N
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Journal Title
PLoS ONE
Volume: 9
Pages: e107867
DOI
Peer Reviewed
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[Journal Article] Distribution of intravenously administered acetylcholinesterase inhibitor and acetylcholinesterase activity in the adrenal gland: 11C-donepezil PET study in the normal rat.2014
Author(s)
Watabe T, Naka S, Ikeda H, Horitsugi G, Kanai Y, Isohashi K, Ishibashi M, Kato H, Shimosegawa E, Watabe H, Hatazawa J.
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Journal Title
PLoS One.
Volume: 9
Pages: e107427.
DOI
Peer Reviewed / Open Access
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[Journal Article] Quantitative assessment of rest and acetazolamide CBF using quantitative SPECT reconstruction and sequential administration of (123)I-iodoamphetamine: comparisonamong data acquired at three institutions.2014
Author(s)
Yamauchi M, Imabayashi E, Matsuda H, Nakagawara J, Takahashi M, Shimosegawa E, Hatazawa J, Suzuki M, Iwanaga H, Fukuda K, Iihara K, Iida H.
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Journal Title
Ann Nucl Med.
Volume: 28
Pages: 836-850
DOI
Peer Reviewed / Open Access
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[Journal Article] Persistent release of IL-1s from skin is associated with systemic cardio-vascular disease, emaciation and systemic amyloidosis: the potential of anti-IL-1 therapy for systemic inflammatory diseases.2014
Author(s)
Yamanaka K, Nakanishi T, Saito H, Maruyama J, Isoda K, Yokochi A, Imanaka-Yoshida K, Tsuda K, Shimaoka M, Mizutoni H, et al.
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Journal Title
PLoS One
Volume: 9
Pages: e104479
DOI
Peer Reviewed
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[Journal Article] Application of encoded library technology (ELT) to a protein-protein interaction target: discovery of a potent class of integrin lymphocyte function- associated antigen 1 (LFA-1) antagonists.2014
Author(s)
Kollmann CS, Bai X, Tsai CH, Yang H, Lind KE, Skinner SR, Zhu Z, Israel DI, Shimaoka M, Evindar G, et al.
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Journal Title
Bioorg Med Chem
Volume: 22
Pages: 2353-2365
DOI
Peer Reviewed
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[Presentation] Evaluation of Recovery Coefficient for Various Positron Emitters in Preclinical Scanner.2014
Author(s)
Kamiya T, Watabe T, Horitsugi G, Matsunaga K, Kanai Y, Ikeda H, Kato H, Ishibashi M, Isohashi K, Shimosegawa E, Fujino K, Hatazawa J.
Organizer
The 4th Annual International ASNMT Conference
Place of Presentation
Osaka, Japan.
Year and Date
2014-11-05
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[Presentation] Quantitative PET imaging of intratumoral oxygen metabolism in hypoxic lesions: comparison study of 18F-FMISO and 15O-labeled gas inhalation PET.2014
Author(s)
Watabe T, Kanai Y, Ikeda H, Horitsugi G, Matsunaga K, Kato H, Isohashi K, Abe K, Shimosegawa E, Hatazawa J.
Organizer
27th Annual Congress of the European Association of Nuclear Medicine (EANM2014)
Place of Presentation
Gothenburg, Sweden
Year and Date
2014-10-18 – 2014-10-22
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[Presentation] Early treatment effects with anti-CD20 immunotherapy in aggressive non-Hodgkin lymphoma: Histopathological, MR-based morphometric, and FDG PET/CT-based metabolic studies in nude rats.2014
Author(s)
Isohashi K, Fukushima K, Watabe T, Kanai Y, Horitsugi G, Ikeda H, Kato H, Tatsumi M, Shimosegawa E, Hatazawa J.
Organizer
27th Annual Congress of the European Association of Nuclear Medicine (EANM2014)
Place of Presentation
Gothenburg, Sweden
Year and Date
2014-10-18 – 2014-10-22
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[Presentation] Prediction of tissue concentration C-11 Donepezil is difficult: Using PET microdosing-wholebody dynamic study in human.2014
Author(s)
Mochida I, Isohashi1 K, Kanai Y, Naka S, Horitugi G, Shimosegawa E, Watabe T, Ishibashi K, Kato H, Hataz
Organizer
27th Annual Congress of the European Association of Nuclear Medicine (EANM2014)
Place of Presentation
Gothenburg, Sweden
Year and Date
2014-10-18 – 2014-10-22
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[Presentation] Astrocytic energy metabolism in rats after cerebral ischemia: 11C-acetate PET study.2014
Author(s)
Matsunaga K., Watabe T, Kanai Y, Horitsugi G, Ikeda H, Kato H, Naka S, Isohashi K,. Shimosegawa E, Hatazawa J.
Organizer
27th Annual Congress of the European Association of Nuclear Medicine (EANM2014)
Place of Presentation
Gothenburg, Sweden
Year and Date
2014-10-18 – 2014-10-22
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[Presentation] In vivo MRI monitoring of inflammatory alterations and cellular dynamics in the central nervous system.2014
Author(s)
Mori Y, Arima Y, Chen T, Zhu D, Komai Y, Nurakami M, Yoshioka Y, Fujisawa T, Kobashi S, Hata
Organizer
World Automation Congress 2014
Place of Presentation
Kona, Hawaii, USA
Year and Date
2014-08-06
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[Presentation] Difference in 4-borono-2-18F-fluoro-phenylalanine kinetics between tumor and inflammation in rat model.2014
Author(s)
Hanaoka K, Watabe T, Naka S, Kanai Y, Horitsugi G,.Ikeda H, Isohashi K, Kato H, Shimosegawa E, Hatazawa J.
Organizer
16th International Congress on Neutron Capture Therapy
Place of Presentation
Helsinki, Finland
Year and Date
2014-06-14 – 2014-06-19
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[Presentation] Quantitative PET imaging of intratumoral oxygen metabolism by 15O-labeled gas inhalation PET.2014
Author(s)
Watabe T, Horitsugi G, Kanai Y, Ikeda H, Kato H, Hanaoka K, Naka S, Isohashi K, Shimosegawa E, Hatazawa J.
Organizer
Society of Nuclear Medicine and Molecular Imaging's 61st Annual Meeting (SNMMI 2014).
Place of Presentation
St Louis, U.S.A.
Year and Date
2014-06-07 – 2014-06-12
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[Presentation] Detection of altered astrocyte activity in multiple sclerosis patients with C-11 acetate PET.2014
Author(s)
Kato H, Takata K, Shimosegawa E, Isohashi K, Watabe T, Tatsumi M, Kanai Y, Naka S, Nakatsuji Y, Hatazawa J.
Organizer
Society of Nuclear Medicine and Molecular Imaging's 61st Annual Meeting (SNMMI 2014).
Place of Presentation
St Louis, U.S.A.
Year and Date
2014-06-07 – 2014-06-12
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[Presentation] Comparison of reconstruction methods for quantitative evaluation in 15O-gas PET study of small animals.2014
Author(s)
Horitsugi G, Watabe T, Kanai Y, Ikeda H, Kato H, Naka S, Ishibashi M, Isohashi K, Shimosegawa E, Hatazawa J.
Organizer
Society of Nuclear Medicine and Molecular Imaging's 61st Annual Meeting (SNMMI 2014).
Place of Presentation
St Louis, U.S.A.
Year and Date
2014-06-07 – 2014-06-12
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[Presentation] Quantitative assessment of myocardial blood flow and coronary flow reserve using adenosine A2A agonist CGS-21680: 13N-Ammonia PET study in normal2014
Author(s)
Ishibashi M, Watabe T, Horitsugi G, Ikeda H, Naka S, Kanai Y, Isohashi K, Kato H, Shimosegawa E, Hatazawa J.
Organizer
Society of Nuclear Medicine and Molecular Imaging's 61st Annual Meeting (SNMMI 2014).
Place of Presentation
St Louis, U.S.A.
Year and Date
2014-06-07 – 2014-06-12
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[Presentation] Prediction of tissue concentration C-11 Donepezil. Using PET microdosing - whole body dynamic study in human.2014
Author(s)
Mochida I, Isohashi K, Kanai Y, Naka Y, Horitugi G, Shimosegawa E, Watabe T, Ishibashi M, Kato H, Hatazawa J.
Organizer
Society of Nuclear Medicine and Molecular Imaging's 61st Annual Meeting (SNMMI 2014).
Place of Presentation
St Louis, U.S.A.
Year and Date
2014-06-07 – 2014-06-12
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[Presentation] Quantitative measurement of cerebral blood flow and oxygen metabolism in small animals with 15O gas inhalation PET: a comparison between arterial blood sampling and image derived input function.2014
Author(s)
Kamiya T, Watabe T, Horitsugi G, Matsunaga K, Kanai Y, Ikeda H, Kato H, Ishibashi M, Isohashi K, Shimosegawa E, Hatazawa J.
Organizer
Society of Nuclear Medicine and Molecular Imaging's 61st Annual Meeting (SNMMI 2014).
Place of Presentation
St Louis, U.S.A.
Year and Date
2014-06-07 – 2014-06-12
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[Presentation] Sequential and time-lapse MRI monitoring of peripheral macrophage recruitment and migration in mouse brain.2014
Author(s)
Mori Y, Chen T, Ohno K, Yoshida S, Tago Y, Fujisawa T, Kashiwagi Y, Fukunaga M, Komai Y, Hata Y, Yoshioka Y
Organizer
The 22nd Annual Meeting of International Society for Magnetic Resonance in Medicine
Place of Presentation
Milan, Italy
Year and Date
2014-05-13
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[Presentation] New Magnetic Nanoparticle for Kidney Function.2014
Author(s)
Yoshioka Y, Chen T, Mori Y, Cheng Z, Kashiwagi Y, Fukunaga M, Kida I, Tago Y, Yoshida S, Ohno K
Organizer
The 22nd Annual Meeting of International Society for Magnetic Resonance in Medicine
Place of Presentation
Milan, Italy
Year and Date
2014-05-13
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