| Laparotomy and burst suppression-inducing sevoflurane induce subtle long-term changes in anxiety and social behavior in late postnatal mice |
|
Tao Zhang1,2, Yulim Lee1,2, Xianshu Ju1, Jiho Park3,4, Boohwi Hong4,5, Jianchen Cui6, Yeonsu Kim7, Seongeun Kim7, Chul Hee Choi1,2,8, Jun Young Heo1,2,9, Woosuk Chung1,2,4,5 |
1Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea
2Brain Korea 21 FOUR Project for Medical Science, Chungnam National University, Daejeon, South Korea
3Department of Anaesthesiology and Pain Medicine, Chungnam National University Sejong Hospital, Sejong, South Korea
4Department of Anaesthesiology and Pain Medicine, Chungnam National University School of Medicine, Daejeon, South Korea
5Department of Anaesthesiology and Pain Medicine, Chungnam National University Hospital, Daejeon, South Korea
6Department of Anaesthesiology, The First People’s Hospital of Yunnan Province. The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
7Department of Applied Artificial Intelligence, Seoul National University of Science and Technology (SeoulTech), Seoul, South Korea
8Department of Microbiology, Chungnam National University School of Medicine, Daejeon, South Korea
9Department of Biochemistry, Chungnam National University School of Medicine, Daejeon, South Korea |
Corresponding author:
Jun Young Heo, Tel: +82-010-6410-6384,
Email: junyoung3@cnu.ac.kr
Woosuk Chung, Tel: +82-010-3420-0698,
Email: woosuk119@cnu.ac.kr
|
|
Received: 31 October 2024 • Revised: 27 March 2025 • Accepted: 30 March 2025 |
|
|
| Abstract |
Background
Despite strong preclinical evidence, clinical studies have reported minimal effects of early anesthesia on neurodevelopment. This discrepancy may be due to limitations of preclinical studies, including the absence of clear criteria for appropriate anesthetic depth, lack of physiological monitoring, and absence of a surgical insult. Therefore, we aimed to evaluate the effects of sevoflurane in a more clinically relevant setting by addressing these known limitations.
Methods
After confirming robust burst suppression (BS) at 2.5% sevoflurane, postnatal day 17 (PND17) mice were assigned to three groups: a Control group, no intervention; BS (-) group, surgery with 1.4% sevoflurane; and a BS (+) group, surgery with 1.4–2.5% sevoflurane. Total duration of anesthesia was 2 h, and blood pressure was non-invasively measured in a subset of mice. Long-term behavioral changes were evaluated from PND56 to PND62 at a two-day interval.
Results
We found subtle but significant changes in anxiety and sociability only in BS (+) group mice. Change in anxiety level was observed in the light/dark box test, with the number of transitions between chambers significantly lower in the BS (+) group (P = 0.025). Reduced sociability was observed in the three-chamber test, as mice in the BS (+) group did not significantly prefer the chamber containing a stranger mouse (P = 0.065).
Conclusions
Both surgery and excessive anesthesia depth are necessary to induce subtle yet long-term behavioral changes in young mice. Future preclinical studies should reconsider sevoflurane concentration and account for surgical trauma as a significant factor when investigating anesthesia-induced neurotoxicity. |
| Key Words:
Anesthesia; Burst suppression; Electroencephalography; Neurodevelopment; Neurotoxicity; Surgery |
|
PDF Links
Full text via DOI
Download Citation
