Laparotomy and burst suppression-inducing sevoflurane induce subtle long-term changes in anxiety and social behavior in late postnatal mice

Tao Zhang ^1,2, Yulim Lee ^1,2, Xianshu Ju ¹

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.

⁰Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea.

Korean Journal of Anesthesiology +

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April 9, 2025

View abstract on PubMed

Summary

Anesthesia depth and surgery combined, not anesthesia alone, caused subtle long-term behavioral changes in young mice, impacting anxiety and sociability. This highlights the need to consider surgical trauma in anesthesia neurotoxicity studies.

Area Of Science

Neuroscience
Anesthesiology
Developmental Biology

Background

Clinical studies show minimal neurodevelopmental effects from early anesthesia, contrasting preclinical findings.
Preclinical models often lack criteria for anesthetic depth, physiological monitoring, and surgical insult, limiting relevance.
This study addresses these limitations to evaluate sevoflurane's impact in a more clinically relevant setting.

Purpose Of The Study

To investigate the neurodevelopmental effects of sevoflurane anesthesia in young mice.
To determine if anesthetic depth and surgical trauma contribute to long-term behavioral changes.
To establish a more clinically relevant preclinical model for anesthesia neurotoxicity research.

Main Methods

Postnatal day 17 mice were exposed to sevoflurane anesthesia for 2 hours.
Three groups were used: Control (no intervention), Burst Suppression (-) (surgery with light anesthesia), and Burst Suppression (+) (surgery with deep anesthesia).
Behavioral changes in anxiety and sociability were assessed long-term using the light/dark box and three-chamber tests.

Main Results

Deep anesthesia combined with surgery (BS (+) group) induced subtle but significant changes in anxiety and sociability.
Anxiety levels increased, indicated by fewer transitions in the light/dark box test (P = 0.025).
Sociability decreased, with mice showing no significant preference for a stranger mouse in the three-chamber test (P = 0.065).

Conclusions

Both surgical trauma and excessive anesthetic depth are required to induce subtle, long-term behavioral changes in young mice.
Future preclinical research on anesthesia-induced neurotoxicity must account for surgical factors and anesthetic depth.
Sevoflurane concentration and surgical insult are critical variables in understanding anesthesia's effects on neurodevelopment.

Keywords:

Anesthesia Burst suppression Electroencephalography Neurodevelopment Neurotoxicity Surgery