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Damage-associated molecular patterns as a mechanism of sevoflurane-induced neuroinflammation in neonatal rodents.
- Source :
-
Korean journal of anesthesiology [Korean J Anesthesiol] 2024 Aug; Vol. 77 (4), pp. 468-479. Date of Electronic Publication: 2024 Apr 01. - Publication Year :
- 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.<br />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.<br />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.<br />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.
- Subjects :
- Animals
Rats
Methyl Ethers toxicity
Male
Brain drug effects
Brain metabolism
Sevoflurane toxicity
Sevoflurane pharmacology
Sevoflurane administration & dosage
Anesthetics, Inhalation toxicity
Anesthetics, Inhalation administration & dosage
Animals, Newborn
Rats, Sprague-Dawley
Neuroinflammatory Diseases chemically induced
Neuroinflammatory Diseases metabolism
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2005-7563
- Volume :
- 77
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Korean journal of anesthesiology
- Publication Type :
- Academic Journal
- Accession number :
- 38556956
- Full Text :
- https://doi.org/10.4097/kja.23796