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Neurotoxicity of general anesthetics in the developing brain

Research Project

Project/Area Number 25293331
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Anesthesiology
Research InstitutionNational Defense Medical College

Principal Investigator

KAZAMA TOMIEI  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, その他部局等, 教授 (40158837)

Co-Investigator(Kenkyū-buntansha) 佐藤 泰司  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, その他部局等, 准教授 (10505267)
神尾 陽子  国立研究開発法人国立精神・神経医療研究センター, その他部局等, その他 (00252445)
照井 克生  埼玉医科大学, 医学部, 教授 (90256074)
鈴木 康之  国立研究開発法人国立成育医療研究センター, その他部局等, その他 (60179265)
遠藤 昌吾  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), その他部局等, その他 (60192514)
中田 隆博  常葉大学, 公私立大学の部局等, 教授 (40273932)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords全身麻酔薬 / 発達期 / 神経毒性 / 自閉症 / マウス / 水素 / 母性行動 / 麻酔 / 小児 / 発達 / 脳 / ERK / ノックアウトマウス / 神経発達 / 細胞内情報伝達 / 臨界期 / ERK / セボフルラン / 行動実験
Outline of Final Research Achievements

In animal models, exposure to general anesthetics induces widespread increases in neuronal apoptosis in the developing brain. Subsequently, abnormalities in brain functioning are found as adulthood, long after the anesthetic exposure. Here we found that female mice that received neonatal exposure to sevoflurane in the developing period had impairments in maternal behaviors, indicating pervasive deficits in brain functioning. We also found that sevoflurane exposure in the developing period increased oxidative stress and mice co-administered of hydrogen gas as antioxidant during sevoflurane exposure did not exhibit the behavioral deficits. We also investigate whether there is an association between early childhood anesthesia exposure and the development of autistic traits in humans. However, no significant difference was found between autistic traits of male children who received anesthesia under 4 years of age and age-matched population sample.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (40 results)

All 2017 2016 2015 2014 2013 Other

All Int'l Joint Research (2 results) Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (20 results) (of which Int'l Joint Research: 2 results,  Invited: 10 results) Book (8 results)

  • [Int'l Joint Research] IRCAN, University of Nice(フランス)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Centre Scientifique de Monaco (CSM)(モナコ)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] The Pharmacokinetics of Atomized Lidocaine Administered via the Trachea: A Randomized Trial2016

    • Author(s)
      Takaenoki Yumiko, Masui Kenichi,Oda Yutaka, Kazama Tomiei
    • Journal Title

      Anesthesia and Analgesia

      Volume: 123 Issue: 1 Pages: 74-81

    • DOI

      10.1213/ane.0000000000001317

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of ERK phosphorylation through oxidative stress is involved in the mechanism underlying sevoflurane-induced toxicity in the developing brain2016

    • Author(s)
      Yufune S, Satoh Y, Akai R, Yoshinaga Y, Kobayashi Y., Endo S, Kazama T.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 21859-21859

    • DOI

      10.1038/srep21859

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Transient Blockade of ERK Phosphorylation in the Critical Period Causes Autistic Phenotypes as an Adult in Mice2015

    • Author(s)
      Yufune S., Satoh Y., Takamatsu I., Ohta H., Kobayashi Y., Takaenoki Y., Pagès G, Pouysségur J, Endo S, and Kazama T.
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 10252-10252

    • DOI

      10.1038/srep10252

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Acute transverse myelitis arising after combined general and thoracic epidural anesthesia2015

    • Author(s)
      Shimada T., Yufune S., Tanaka M., Akai R., Satoh Y., and Kazama T
    • Journal Title

      JA Clinical Reports

      Volume: 1 Issue: 1 Pages: 4-4

    • DOI

      10.1186/s40981-015-0006-5

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful resuscitation of amniotic fluid embolism applying a new classification and management strategy2015

    • Author(s)
      Yufune S., Tanaka M., Akai R., Satoh Y., Furuya K., Terui K., and Kazama T
    • Journal Title

      JA Clinical Reports

      Volume: 1 Issue: 1 Pages: 1-1

    • DOI

      10.1186/s40981-015-0001-x

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neonatal exposure to sevoflurane in mice causes deficits in maternal behavior later in adulthood.2014

    • Author(s)
      Takaenoki Y, Satoh Y, Araki Y, Kodama M, Yonamine R, Yufune S, Kazama T.
    • Journal Title

      Anesthesiology.

      Volume: 120(2) Issue: 2 Pages: 403-15

    • DOI

      10.1097/aln.0000435846.28299.e7

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Targeted deletion of ERK2 in cardiomyocytes attenuates hypertrophic response but provokes pathological stress induced cardiac dysfunction.2014

    • Author(s)
      Ulm S, Liu W, Zi M, Tsui H, Chowdhury SK, Endo S, Satoh Y, Prehar S, Wang R, Cartwright EJ, Wang X.
    • Journal Title

      J Mol Cell Cardiol

      Volume: 72C Pages: 104-116

    • DOI

      10.1016/j.yjmcc.2014.03.002

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatic extracellular signal-regulated kinase 2 suppresses endoplasmic reticulum stress and protects from oxidative stress and endothelial dysfunction2013

    • Author(s)
      Kujiraoka T, Satoh Y, Ayaori M, Shiraishi Y, Arai-Nakaya Y, Hakuno D, Yada H, Kuwada N, Endo S, Isoda K, Adachi T.
    • Journal Title

      J Am Heart Assoc

      Volume: 2 Issue: 4

    • DOI

      10.1161/jaha.113.000361

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pulse wave transit time measurements of cardiac output in patients undergoing partial hepatectomy: a comparison of the esCCO system with thermodilution.2013

    • Author(s)
      Tsutsui M, Araki Y, Masui K, Kazama T, Sugo Y, Archer TL, Manecke GR Jr.
    • Journal Title

      Anesth Analg.

      Volume: 117 Issue: 6 Pages: 1307-1312

    • DOI

      10.1213/ane.0b013e3182a44c87

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deep cerebellar nuclei play an important role in two-tone discrimination on delay eyeblink conditioning in C57BL/6 mice.2013

    • Author(s)
      Sakamoto, T., and Endo, S.
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 3 Pages: e59880-e59880

    • DOI

      10.1371/journal.pone.0059880

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Neurotoxicity of general anesthetics in the critical period and strategy for its prevention2017

    • Author(s)
      Yasushi Satoh
    • Organizer
      21th Annual Meeting of Korean Society of Obstetric Anesthesiologists
    • Place of Presentation
      大韓民国
    • Year and Date
      2017-06-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 麻酔薬の発達段階の脳に対する神経毒性のメカニズムと脳保護戦略2017

    • Author(s)
      佐藤泰司
    • Organizer
      第64回日本麻酔科学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2017-06-08
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Neurotoxicity of general anesthetics in the critical period and strategy for its prevention2017

    • Author(s)
      Yasushi Satoh
    • Organizer
      the First Jinling International Anesthesia and Brain Function Forum
    • Place of Presentation
      中華人民共和国
    • Year and Date
      2017-05-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 臨界期における全身麻酔薬の神経発達制御メカニズムへ及ぼす影響2016

    • Author(s)
      佐藤泰司
    • Organizer
      第4回新胎児学研究会
    • Place of Presentation
      大津
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 脳と水素2016

    • Author(s)
      佐藤泰司
    • Organizer
      第20回日本医療ガス学会学術大会
    • Place of Presentation
      秋田
    • Year and Date
      2016-10-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 発達期マウスへのデスフルランとセボフルラン曝露が母性行動に及ぼす影響の比較2016

    • Author(s)
      高榎由美子
    • Organizer
      日本麻酔科学会 第63回学術集会
    • Place of Presentation
      マリンメッセ福岡
    • Year and Date
      2016-05-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 発達期マウスのセボフルラン毒性メカニズムにおける細胞外シグナル調節キナーゼの役割2016

    • Author(s)
      吉川幸尾
    • Organizer
      日本麻酔科学会 第63回学術集会
    • Place of Presentation
      マリンメッセ福岡
    • Year and Date
      2016-05-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Roles of ERK for the development of neuronal functions2016

    • Author(s)
      佐藤泰司
    • Organizer
      第89回日本薬学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 神経発達とセボフルラン2015

    • Author(s)
      佐藤泰司、湯舟晋也、風間富栄
    • Organizer
      日本麻酔科学会第62回学術集会
    • Place of Presentation
      神戸ポートピアホテル(兵庫県神戸市)
    • Year and Date
      2015-05-28 – 2015-05-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 小児麻酔の神経毒性に関する研究-小児麻酔の安全性向上のために-2015

    • Author(s)
      佐藤泰司
    • Organizer
      日本麻酔科学会第62回学術集会
    • Place of Presentation
      神戸ポートピアホテル(兵庫県神戸市)
    • Year and Date
      2015-05-28 – 2015-05-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] 神経発達とセボフルラン2015

    • Author(s)
      Yasushi Satoh
    • Organizer
      日本麻酔科学会 第62回学術集会
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2015-05-28
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 小児麻酔の神経毒性に関する研究-小児麻酔の安全性向上のために-2015

    • Author(s)
      佐藤泰司
    • Organizer
      日本麻酔科学会 第62回学術集会
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2015-05-28
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Molecular hydrogen suppresses apoptosis in neurons and oligodendrocyte caused by neonatal exposure to general anesthetics in mice2014

    • Author(s)
      Yufune S., Satoh Y., Shimada T., Yonamine R., Kazama T.
    • Organizer
      2014年 北米神経科学会
    • Place of Presentation
      ワシントンDC(米国)
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Innnate behavior is impaired by neonatal exposure to sevoflurane in mice2014

    • Author(s)
      Satoh Y.,Takaenoki Y., Kazama T.
    • Organizer
      欧州小児麻酔学会
    • Place of Presentation
      プラハ(チェコ)
    • Year and Date
      2014-09-18 – 2014-09-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Innate behavior is impaired by neonatal exposure to general anesthetics in mice.2014

    • Author(s)
      Satoh Y.,Takaenoki Y., Kazama T.
    • Organizer
      欧州麻酔学会
    • Place of Presentation
      ストックホルム(スウェーデン)
    • Year and Date
      2014-05-31 – 2014-06-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] 水素ガスは発達期脳に対するデスフルランの毒性を軽減する2014

    • Author(s)
      嶋田哲也、与那嶺龍二、佐藤泰司、風間富栄
    • Organizer
      日本麻酔科学会第61回学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 幼弱期のマウスのセボフルラン曝露が母性行動に及ぼす影響2014

    • Author(s)
      石井絵里香、高榎由美子、川口早織、佐藤泰司、風間富栄
    • Organizer
      日本麻酔科学会第61回学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 動物実験によって暴かれた麻酔薬の未知の毒性-麻酔薬の神経発達への影響2013

    • Author(s)
      佐藤泰司、風間富栄
    • Organizer
      日本麻酔科学会第60回学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 発達期の脳に対する 麻酔薬の神経毒性について -育児放棄とセボフルランの関係-2013

    • Author(s)
      佐藤泰司
    • Organizer
      日本小児麻酔学会 第19回大会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Hydrogen gas suppresses neuronal apoptosis and subsequent behavioral deficits caused by neonatal exposure to general anesthetics in mice2013

    • Author(s)
      Yonamine R, Satoh Y, Kodama M, Kazama T.
    • Organizer
      2013北米神経科学会
    • Place of Presentation
      米国、サンディエゴ
    • Related Report
      2013 Annual Research Report
  • [Book] Anesthesia and Neurotoxicity "Clinical findings including prevention and treatment"2017

    • Author(s)
      Yasushi Satoh
    • Total Pages
      15
    • Publisher
      Springer Japan
    • Related Report
      2016 Annual Research Report
  • [Book] エビデンスで読み解く小児麻酔 「麻酔薬の神経毒性」2016

    • Author(s)
      佐藤泰司
    • Total Pages
      7
    • Publisher
      克誠堂出版
    • Related Report
      2016 Annual Research Report
  • [Book] Anesthesia and Neurotoxicity2016

    • Author(s)
      Yasushi Satoh
    • Total Pages
      10
    • Publisher
      シュプリンガー・ジャパン
    • Related Report
      2015 Annual Research Report
  • [Book] Clinical Neuroscience2013

    • Author(s)
      佐藤泰司、遠藤昌吾
    • Total Pages
      97
    • Publisher
      中外医学社
    • Related Report
      2013 Annual Research Report
  • [Book] Clinical Neuroscience2013

    • Author(s)
      佐藤泰司
    • Total Pages
      97
    • Publisher
      中外医学社
    • Related Report
      2013 Annual Research Report
  • [Book] レジデント2013

    • Author(s)
      風間富栄
    • Total Pages
      136
    • Publisher
      医学出版
    • Related Report
      2013 Annual Research Report
  • [Book] LiSA2013

    • Author(s)
      風間富栄
    • Total Pages
      83
    • Publisher
      メディカルサイエンスインターナショナル
    • Related Report
      2013 Annual Research Report
  • [Book] Clinical Neuroscience2013

    • Author(s)
      遠藤昌吾
    • Total Pages
      97
    • Publisher
      中外医学社
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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