The role of GABA modulators on the brain function

• Project/Area Number: 18K08820
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Nishikawa Koichi 福島県立医科大学, 公私立大学の部局等, 博士研究員 (00334110)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2022: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: GABA / 麻酔 / 麻酔効果 / 個人差 / 受容体 / プロポフォール / シナプス可塑性 / GABA 受容体 / 鎮静 / 鎮痛 / 発達期の脳 / 神経毒性 / 麻酔薬

Outline of Final Research Achievements

Extra-synaptic γ-aminobutyric acid (GABA) receptors appear to be an important target of general anesthetics. We have reported ambient GABA concentrations, which contribute to tonic inhibition, as an important determinant of the hypnotic actions of the intravenous anesthetic propofol. These data suggest that manipulations of ambient GABA concentrations could also affect the amnestic properties of propofol. Genetic and pharmacological manipulations designed to alter ambient GABA concentrations affect propofol inhibition of hippocampal LTP and this supports evidence that effects on tonic GABA currents contribute to the amnestic properties of propofol.

Academic Significance and Societal Importance of the Research Achievements

麻酔薬の鎮静・鎮痛・健忘作用など多くの作用に細胞外GAB濃度の変化が重要な役割を担っている。したがって細胞外GABA濃度が変化するような病態(痛み・ストレス・性周期など)で、麻酔薬の作用が変化することが判明した。今回の研究成果から、臨床の現場でもこれらの仮説の正当性が確認された。

Research Products

• [Journal Article] It was not a fall, but fainting: A case report of pulmonary embolism (2020)
  • Author(s): Fujita Yoshihisa、Shimada Kumi、Nishikawa Koichi
  • Journal Title: FUKUSHIMA JOURNAL OF MEDICAL SCIENCE Volume: 66 Issue: 2 Pages: 113-117
  • DOI: 10.5387/fms.2020-05
  • NAID: 130007884401
  • ISSN: 0016-2590, 2185-4610
  • Peer Reviewed
• [Journal Article] Successful perioperative management of a patient with erythropoietin-producing uterine myoma. (2018)
  • Author(s): Kobayashi M, Akatsu M, Fujita Y, Nishikawa K
  • Journal Title: JA Clinical Reports Volume: 4 Pages: 50-50
  • Peer Reviewed
• [Presentation] Pulmonary thromboembolism diagnosed with point of care ultrasonography in the operating room. (2019)
  • Author(s): Fujita Y, Shimada K, Nishikawa K
  • Organizer: ESRA 2019
  • Int'l Joint Research
• [Presentation] Slightly more time is necessary to achieve neuraxial anesthesia in obese patients for cesarean section. (2019)
  • Author(s): 179.Fujita Y, Akatsu M, Nishikawa K, Sanpei M, Honda T
  • Organizer: ESRA 2019
  • Int'l Joint Research
• [Presentation] 腹部手術後、先天性気管狭窄と診断された新生児の1症例. (2018)
  • Author(s): 佐藤 友彦、遠藤 千麻、石堂 瑛美、藤田 喜久、赤津 賢彦、西川 光一
  • Organizer: 日本麻酔科学会・関東甲信越・東京支部第58回合同学術集会
• [Presentation] 喉頭嚢胞の手術に際し気道確保困難が予想された患者にエアウェイスコープ（AWS）を用い安全に管理できた２症例. (2018)
  • Author(s): 遠藤 千麻、島田 久美、若原 志保、藤田 喜久、赤津 賢彦、西川 光一
  • Organizer: 日本麻酔科学会・北海道・東北支部第8回学術集会