Effects of Olanzapine on postoperative cognitive dysfunction

2019 Fiscal Year Final Research Report

• Project/Area Number: 15K10531
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: University of Tsukuba
• Principal Investigator: Fukuda Taeko 筑波大学, 医学医療系, 教授 (40228911)
• Project Period (FY): 2015-10-21 – 2020-03-31
• Keywords: 術後認知障害

Outline of Final Research Achievements

Six-month-old male rats were underwent laparotomy and intra-peritoneal injection of lipopolysaccharide (LPS) or LPS + olanzapine for preparing a postoperative cognitive dysfunction model. Behavior observation and a maze test were performed the next day. In the Burns maze test, the LPS + olanzapine group showed significantly better results than the LPS group, which effect was similar degree to the control group that was anesthetized but not operated.
Immunohistochemical study of hippocampal microglial activity revealed that olanzapine significantly suppressed hippocampal microglial activity. On the other hand, no difference was observed in the blood cytokine measurement between the LPS and LPS + olanzapine groups.It was speculated that olanzapine has a neuroprotective / repair effect rather than a direct suppression of cytokine production.

Free Research Field

麻酔科

Academic Significance and Societal Importance of the Research Achievements

今回の研究目的は、現在術後回復の大きな障害となっている術後認知障害の動物モデルを作成し、向精神薬オランザピンの効果を検証することにあった。比較的若年のラットで術後認知障害モデルを作成することは困難であったが、開腹手術と腸管操作及びリポポリサッカロイド（LPS)の組み合わせによって動物モデルを作成することができた。
オランザピンの投与は術後認知障害を抑制し、懸念されていた高血糖も観察されなかった。オランザピンには、鎮痛作用や鎮静作用があるので、今後術後認知障害を予防する薬剤の一候補となる可能性が示唆される結果となった。