Korean Journal of Anesthesiology

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Experimental Research Article

DOI: https://doi.org/10.4097/kja.23796
Damage-associated molecular patterns as a mechanism of sevoflurane-induced neuroinflammation in neonatal rodents
Young-Eun Joe1  , Ji Hae Jun2  , Ju Eun Oh2  , Jeong-Rim Lee3 
1Department of Anesthesiology and Pain Medicine, Asan Medical Center, Seoul, Korea
2Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea
3Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea
Corresponding author: Ju Eun Oh ,Tel: +82-2-2228-2810, Fax: +82-2-2227-6517, Email: JEOH0405@yuhs.ac
Jeong-Rim Lee ,Tel: +82-2-2228-2420, Fax: +82-2-2227-7897, Email: manya@yuhs.ac
Received: November 1, 2023; Revised: March 14, 2024   Accepted: March 17, 2024.
Abstract
Background
General anesthesia is inevitable for pediatric patients undergoing surgery, though volatile anesthetic agents may cause neuroinflammation and neurodevelopmental impairment; however, the underlying pathophysiology remains unclear. We aimed to investigate the neuroinflammation mechanism in developing rat brains associated with sevoflurane exposure time, by identifying the specific damage-associated molecular patterns (DAMPs) pathway and evaluating the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in alleviating neuroinflammation.
Methods
A three-step experiment was conducted to investigate neuroinflammation induced by sevoflurane. First, the exposure time required for sevoflurane to cause neuroinflammation was determined. Next, the specific pathways of DAMPs involved in neuroinflammation by sevoflurane were identified. Finally, the effects of NSAIDs on sevoflurane-induced neuroinflammation were investigated. The expression of various molecules in the rat brain were assessed using immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, western blot analysis, and enzyme-linked immunosorbent assay.
Results
In total, 112 rats (aged 7 days) were used, of which six rats expired during the experiment (mortality rate, 5.3%). Expression of CD68, HMGB-1, galectin-3, TLR4, TLR9, and phosphorylated NF-κB was significantly increased upon 6 h of sevoflurane exposure. Conversely, transcriptional levels of TNF-α and IL-6 significantly increased and IFN-γ significantly decreased after 6 h of sevoflurane exposure. Co-administration of NSAIDs with sevoflurane anesthesia significantly attenuated TNF-α and IL-6 levels and restored IFN-γ levels.
Conclusions
In conclusion, 6 h of sevoflurane exposure induces neuroinflammation through the DAMPs pathway, HMGB-1, and galectin-3. Co-administration of ibuprofen reduced sevoflurane-induced neuroinflammation.

Keywords :Alarmins; Damage-associated molecular pattern molecules; Galectin 3; HMGB1 protein; Neonate; Non-steroidal anti-inflammatory agents; Rats; Sevoflurane.

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