2022 Fiscal Year Final Research Report
The efficacy and potential mechanisms of rho-kinase inhibitor in postoperative cognitive dysfunction
| Project/Area Number |
20K09237
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55050:Anesthesiology-related
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| Research Institution | Akita University |
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Principal Investigator |
Kimura Tetsu 秋田大学, 医学部附属病院, 准教授 (00312702)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 術後高次脳機能障害 / 神経炎症 / 血液－脳関門 / Rhoキナーゼ阻害薬 |
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| Outline of Final Research Achievements |
We investigated whether fasudil, a Rho-kinase inhibitor, could inhibit postoperative cognitive dysfunction after surgery under general anesthesia in male-aged rats. We also investigated its effects on brain inflammation and functional changes in the blood-brain barrier to clarify some of the mechanisms of its brain-protective effects.
Eighteen months old rats were given sevoflurane for 2 hours and underwent partial hepatic ligation. The Morris water maze and Fear Conditioning tests were performed as behavioral tests before and after surgery. The brain was perfused on the seventh postoperative day to evaluate the wet/dry ratio and the Evans blue leakage.
The collected data are being analyzed, and it is expected to take several months to show the study's results.
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| Free Research Field |
麻酔科学
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| Academic Significance and Societal Importance of the Research Achievements |
術後認知機能障害は手術・麻酔を契機として発症する高次脳機能障害であり、入院期間延長、医療費増大、死亡率増加を招く。高齢者人口の増大に伴う手術件数の増加により、今後増加していくことが懸念される。その発症には神経炎症による血液－脳関門の破綻が関与すると推察されている。Rhoキナーゼ阻害薬であるファスジルは、神経炎症抑制効果により虚血性脳脊髄傷害やアルツハイマー病などの予防、治療薬として有用である可能性が示唆されている。ファスジルは本邦ですでに臨床使用されている薬剤であり、術後高次脳機能障害抑制効果が明らかになれば速やかな臨床応用が期待できる。
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