mechanisms of neuroprotection by general anesthesia

• Project/Area Number: 17K11046
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Gifu University
• Principal Investigator: Tanabe Kumiko 岐阜大学, 大学院医学系研究科, 准教授 (30402209)
• Co-Investigator(Kenkyū-buntansha): 飯田 宏樹 岐阜大学, 大学院医学系研究科, 教授 (30159561)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: アストロサイト / サイトカイン / 脳血管反応 / 全身麻酔薬 / 血管内皮機能 / 血糖値 / 高二酸化炭素血症 / 神経炎症 / 細胞内情報伝達 / 中枢神経保護 / 脳代謝

Outline of Final Research Achievements

Rho-kinase and Rac limit TGF-β-induced IL-6 release from cultured primary astrocytes (C8D1A cells), and the suppressive effects are exerted independently of the Smad pathway or at a point downstream of Smad2/3 complex.
Rat pial arteriole responses to acetylcholine are maintained during conditions of acute hyperglycemia with propofol anesthesia but suppressed compared with normoglycemia with desflurane anesthesia.
Sevoflurane or desflurane dilated pial vessels in a concentration- dependent manner and enhanced hypercapnia-induced cerebrovascular dilation. The rates of vasodilation were similar for sevoflurane and desflurane under both normocapnia and hypercapnia.

Academic Significance and Societal Importance of the Research Achievements

近年、脳虚血後の再灌流障害、神経変性疾患など多くの中枢神経系の疾患に感染を伴わない炎症が関与していることが明らかとなってきた。炎症性サイトカイン遊離機序を解明することにより、中枢神経系の様々な疾患の発症機序の解明と、それらに対する治療薬の開発の一助となる。
全身麻酔薬が脳血管反応に与える影響を検討することで、様々な病態（高血糖時、頭部外傷時、脳手術時など）に合わせた麻酔薬の選択、麻酔管理を可能にできる。

Research Products

• [Journal Article] Propofol but not desflurane maintains rat cerebral arteriolar responses to acetylcholine during acute hyperglycemia (2019)
  • Author(s): Sakata Koji、Kito Kazuhiro、Tanabe Kumiko、Fukuoka Naokazu、Nagase Kiyoshi、Iida Hiroki
  • Journal Title: Journal of Neurosurgical Anesthesiology Volume: EPub Issue: 2 Pages: 177-182
  • DOI: 10.1097/ana.0000000000000632
  • Peer Reviewed
• [Journal Article] Cerebrovascular Reactivity to Hypercapnia During Sevoflurane or Desflurane Anesthesia in Rats (2019)
  • Author(s): Koji Sakata, Kazuhiro Kito, Naokazu Fukuoka, Kiyoshi Nagase, Kumiko Tanabe, Hiroki Iida
  • Journal Title: Korean J Anesthesiol Volume: 72 Issue: 3 Pages: 260-264
  • DOI: 10.4097/kja.d.18.00244
  • Peer Reviewed
• [Journal Article] Limitation by Rho-kinase and Rac of transforming growth factor-β-induced interleukin-6 release from astrocytes (2019)
  • Author(s): Tanabe Kumiko、Kojima Akiko、Tachi Junko、Nakashima Daiki、Kozawa Osamu、Iida Hiroki
  • Journal Title: Neuroscience Letters Volume: 696 Pages: 191-196
  • DOI: 10.1016/j.neulet.2018.12.040
  • Peer Reviewed
• [Presentation] 中枢神経系の虚血/再灌流障害の分子メカニズムと今後の展望 (2019)
  • Author(s): 田辺久美子
  • Organizer: 日本麻酔科学会66回学術集会
• [Presentation] Compatible effect of cilostazol and aspirin on the impairment of endothelium dependent cerebral vasodilation caused by acute hyperglycemia in rats (2019)
  • Author(s): Kazuhiro Kuto
  • Organizer: American Soceity of Anesthesiologists 2019 Annual Meeting
  • Int'l Joint Research
• [Presentation] プロポフォールは急性高血糖時における脳血管のアセチルコリンに対する反応性を保持する (2019)
  • Author(s): 阪田耕治
  • Organizer: 第23回日本神経麻酔集中治療学会
• [Presentation] 急性高血糖に伴う血管内皮依存症血管拡張障害に対するアスピリンとシロスタゾールの保護効果の検討 (2019)
  • Author(s): 鬼頭和裕
  • Organizer: 日本麻酔科学会66回学術集会
• [Presentation] 脳虚血におけるサイトカインの役割と新しい脳保護戦略 (2018)
  • Author(s): 田辺久美子
  • Organizer: 日本麻酔科学会第65回学術集会
• [Presentation] Inhibitors of Rho-kinase or Rac enhance TGF-β-induced IL-6 release from astrocytes (2017)
  • Author(s): Kumioko Tanabe, Hiroki Iida, osamu Kozawa
  • Organizer: The 5th Conference of Asian Society of Neuroanesthesia and critical Care
  • Int'l Joint Research