A novel therapeutic strategy for postoperative cognitive dysfunction by PGC-1a and microRNA

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16737
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Kochi University
• Principal Investigator: Tateiwa Hiroki 高知大学, 教育研究部医療学系臨床医学部門, 助教 (90614397)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 術後認知機能障害 / neuroimflammation / αリポ酸 / BDNF

Outline of Final Research Achievements

Postoperative cognitive dysfunction (POCD) is caused by the neuroinflammation due to surgical invasion.　This condition is generally associated with postoperative QOL deterioration. Recent research suggested that preoperative exercise may be an effective preventive strategy. However, the preoperative exercise approach is often difficult to implement in elderly patients. In this study, we examined whether POCD could be prevented by administering ALA, a substance that induces the protein PGC-1α expressed during exercise.
As a result, PGC-1α and hippocampal BDNF levels increased by preoperatively administering ALA to aged rats. In addition, the novel object recognitive test on POD7 showed that cognitive function was maintained. Furthermore, hippocampal TNF-α levels decreased.
ALA administration suppressed neuroinflammation and prevented the development of POCD.

Free Research Field

麻酔

Academic Significance and Societal Importance of the Research Achievements

高齢化社会の進行および手術技術の向上に伴い、高齢患者が手術を受ける機会が増加している。それに伴い術後認知機能障害(POCD)などの合併症が社会的にも大きな問題となっている。POCDに対して術前の運動が有効である可能性は示唆されているものの、特に高齢患者では困難な場合も少なくない。それに対してαリポ酸の投与により、運動と同等の効果をもたらす可能性がある今研究結果がもたらす意味は大きいと思われる。またαリポ酸はサプリメントとしてもヒトでも使用されているものであり、今後、臨床への応用が期待される。