To elucidate mechanisms of anesthetic-induced neuroprotection and neurotoxicity

2019 Fiscal Year Final Research Report

• Project/Area Number: 15K10512
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: International University of Health and Welfare (2017-2019); Osaka University (2015-2016)
• Principal Investigator: Shibuta Satoshi 国際医療福祉大学, 医学部, 教授 (20324767)
• Project Period (FY): 2015-04-01 – 2020-03-31
• Keywords: 静脈麻酔薬 / 幼弱脳 / 神経毒性 / 神経保護 / 初代培養脳神経細胞 / カルシウムイメージング

Outline of Final Research Achievements

The neurotoxicity of anesthetics in children is currently major concern for not only for anesthesiologists but also patients and their parents. We compared the effects of the intravenous anesthetics, midazolam, propofol, and thiopental sodium on primary cultured neurons along with the course of development.
Although many in vitro studies showed that thiopental sodium is neuroprotective, clinical attempts showed unsatisfactory results. We investigated the dynamics of the intracellular calciumin the surviving neurons after hypoxic insults with or without TPS pretreatment following the application of neurotransmitters. Though TPS was neuroprotective against HI morphologically, the response not to L-glutamate but to acetylcholine was impaired. This may partially explain the inconsistent results regarding the neuroprotective effects of TPS.

Free Research Field

麻酔学

Academic Significance and Societal Importance of the Research Achievements

小児における麻酔薬の神経毒性は、麻酔科医をはじめ、広く社会的にも大きな問題とされ関心を集めている。我々は、ラット胎児大脳皮質神経細胞より初代培養を行い、本邦で汎用されている3種類の静脈麻酔薬をそれぞれ培養日数の異なる神経細胞に投与し、細胞死に到る様子を形態学的手法により調べ、さらに麻酔薬を投与した際の神経細胞内カルシウム濃度を測定することにより、中枢神経の発達に伴う臨床使用濃度における麻酔薬の神経毒性の経時的変化を調べた。
これらの結果、特定の条件下（培養日数及び麻酔薬の種類）では麻酔薬の神経毒性が大きくなることが示唆され、実際の小児麻酔を行う際の麻酔薬の選択に影響を与えるものと考えられる。