The effect of astrocyte inhibitor ONO-2506 for postoperative cognitive function

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08986
• 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: Akita University
• Principal Investigator: Yamamoto Natsuko (工藤夏子) 秋田大学, 医学系研究科, 助教 (40771514)
• Co-Investigator(Kenkyū-buntansha): 安部 恭子 秋田大学, 医学部附属病院, 助教 (30311575) ; 山本 洋平 秋田大学, 医学系研究科, 非常勤講師 (70400512) ; 新山 幸俊 秋田大学, 医学系研究科, 教授 (90423764)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 術後認知機能障害 / アストロサイト / アストロサイト活性化阻害薬 / S100β

Outline of Final Research Achievements

To evaluate the effect of the astrocyte activation inhibitor ONO-2506 (ONO) on postoperative cognitive function in aged rats, we divided the aged rats into four groups: surgery+/ONO+, surgery+/ONO-, surgery-/ONO+ and surgery-/ONO-, where the ONO group received 30 mg/kg and the non-treated group received saline intraperitoneally. Surgery groups underwent open femoral fracture and intramedullary fixation of the left hind limb under 2 hours of sevoflurane anesthesia. Subsequently, neurological outcomes were evaluated using the Morris water maze (MWM) test, and histopathological outcomes were assessed to count the number of S100β-positive astrocytes in hippocampus. The results showed no increase in hippocampal activated astrocytes in the surgical group, but ONO administration significantly reduced S100β-positive astrocytes. There are no significant differences between the groups and ONO administration had no effect on postoperative cognitive function in this study.

Free Research Field

麻酔、神経麻酔

Academic Significance and Societal Importance of the Research Achievements

アストロサイトの異常活性化によって慢性的な脳内炎症が引き起こされ術後認知機能障害（POCD）の原因となるのではないかと仮説を立てたが、手術・麻酔群において活性化アストロサイトの有意な増加は認められなかった。脳内炎症におけるミクログリアの増加は報告があるが、アストロサイトの機能異常がPOCDに影響を及ぼすという報告はこれまで見当たらなかったため、これを証明すれば高齢者のPOCDの予防において新たな方向性が見つかる可能性があった。