Pathophysiology of sepsis-related encephalopathy and investigation of therapeutic agents

• Project/Area Number: 16K10928
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Toho University (2018-2019); Nagoya University (2016-2017)
• Principal Investigator: SATOMOTO Maiko 東邦大学, 医学部, 講師 (10611551)
• Co-Investigator(Kenkyū-buntansha): 槇田 浩史 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (20199657)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 神経炎症 / 認知機能障害 / セボフルラン / 脳 / 脳・神経 / 麻酔 / 敗血症

Outline of Final Research Achievements

Systemic inflammation induces brain neuronal inflammation, in turn causing acute cognitive disorders. Furthermore, neuronal inflammation is one cause of postoperative cognitive disorder (POCD) and delirium. However, no sufficiently established pharmacological treatment is available for neurocognitive inflammation. This study evaluated the possible neuroprotective effects of preconditioning with sevoflurane anesthesia on cognition and neuroinflammatory changes in an animal model of lipopolysaccharide (LPS)-induced systemic inflammation. This study supports the hypothesis that sevoflurane preconditioning might also be beneficial for neuronal inflammation. Sevoflurane might be beneficial for reducing delirium and POCD.

Academic Significance and Societal Importance of the Research Achievements

敗血症を起因とした敗血症性脳症は、全身性炎症反応の結果として生じ、せん妄、見当識障害など様々な症状を呈する。しかしながら、敗血症関連脳症の発生メカニズムは明らかになっておらず、病態機序の解明と治療薬の開発は注目されており臨床的にも喫緊の課題となっている。今回全身性炎症由来の脳内神経炎症と認知機能低下モデルマウスに対して、セボフルランの前投与が全身性LPS投与により引き起こされた記憶障害を改善させ、過度のミクログリアの活性化を抑制し、炎症を抑え、アミロイド関連蛋白の上昇を抑制した。これら結果からセボフルランの前投与は全身炎症性反応の結果引き起こされる脳内神経炎症に有効である可能性が示唆された。

Research Products

• [Journal Article] Blood-brain barrier disruption caused by neonatal sevoflurane-induced depends on exposure time and is reversible in mice (2019)
  • Author(s): Satomoto M, Sun Z, Adachi YU, Makita K.
  • Journal Title: Korean J Anesthesiol. Volume: - Issue: 4 Pages: 389-391
  • DOI: 10.4097/kja.d.19.00029
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dopaminergic pathway modifies anaesthetic properties of propofol: in vivo animal experiments. (2019)
  • Author(s): Adachi YU, Katoh Y, Kuroiwa K, Satomoto M, Tamura T, Sato Boku A.
  • Journal Title: Eur J Anaesthesiol. Volume: 36 (e-supple 57) Pages: 140-140
  • Peer Reviewed
• [Journal Article] Sevoflurane preconditioning ameliorates lipopolysaccharide-induced cognitive impairment in mice (2018)
  • Author(s): 里元麻衣子 孫忠良 足立裕史 木下浩之 槇田浩史
  • Journal Title: Experimental Animals Volume: 67 Issue: 2 Pages: 193-200
  • DOI: 10.1538/expanim.17-0102
  • NAID: 130006733608
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neonatal Sevoflurane Exposure Induces Adulthood Fear-induced Learning Disability and Decreases Glutamatergic Neurons in the Basolateral Amygdala (2018)
  • Author(s): Satomoto Maiko、Sun Zhongliang、Adachi Yushi U.、Makita Koshi
  • Journal Title: J Neurosurg Anesthesiol Volume: 30 Issue: 1 Pages: 59-64
  • DOI: 10.1097/ana.0000000000000387
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Dopaminergic Pathway Modifies Anaesthetic Properties of Propofol: in vivo Animal Experiments (2019)
  • Author(s): Adachi YU, Katogi Y, Kuroiwa K, Satomoto M, Tamura T, Sato Boku A.
  • Organizer: Euroanesthesia 2019
  • Int'l Joint Research
• [Presentation] Midazolam-induced Electroencephalographic Change Is Not Fully Antagonized By Flumazenil During Propofol Anesthesia In Rats. (2019)
  • Author(s): Adachi YU, Higashi M, Taharabaru K, Kuroiwa K, Tamura T, Satomoto M, Sato A, Okuda M.
  • Organizer: Anesthesiology Annual Meeting 2019
  • Int'l Joint Research
• [Presentation] セボフルランの前投与は、LPS投与後の全身性炎症反応による認知機能低下を減弱させる効果がある (2017)
  • Author(s): 里元麻衣子 孫忠良 足立裕史 木下浩之 槇田浩史
  • Organizer: 日本麻酔科学会大64回学術集会
• [Presentation] セボフルランの前投与は、LPS投与後の全身性炎症反応による認知機能低下を減弱させる効果がある (2017)
  • Author(s): 里元麻衣子、孫忠良、張愛玲、足立裕史、槇田浩史
  • Organizer: 日本麻酔科学会第64回学術集会
  • Place of Presentation: 神戸ポートピアホテル(兵庫県神戸市）
• [Book] General Anesthesia Research (2019)
  • Author(s): Maiko Satomoto
  • Total Pages: 255
  • Publisher: Springer Nature
  • ISBN: 9781493998913