Journal article
Damage-associated molecular patterns as a mechanism of sevofluraneinduced neuroinflammation in neonatal rodents
Korean journal of anesthesiology, Vol.77(4), pp.468-479
08/01/2024
DOI: 10.4097/kja.23796
PMCID: PMC11294876
PMID: 38556956
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-kappa B was significantly increased upon 6 h of sevoflurane exposure. Conversely, transcriptional levels of TNF-alpha and IL-6 significantly increased and IFN-gamma significantly decreased after 6 h of sevoflurane exposure. Co-administration of NSAIDs with sevoflurane anesthesia significantly attenuated TNF-alpha and IL-6 levels and restored IFN-gamma 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.
Details
- Title: Subtitle
- Damage-associated molecular patterns as a mechanism of sevofluraneinduced neuroinflammation in neonatal rodents
- Creators
- Young-Eun Joe - Asan Med Ctr, Dept Anesthesiol & Pain Med, Sch Med, Seoul, South KoreaJi Hae Jun - Yonsei UniversityJu Eun Oh - Yonsei UniversityJeong-Rim Lee - Yonsei University
- Resource Type
- Journal article
- Publication Details
- Korean journal of anesthesiology, Vol.77(4), pp.468-479
- DOI
- 10.4097/kja.23796
- PMID
- 38556956
- PMCID
- PMC11294876
- NLM abbreviation
- Korean J Anesthesiol
- ISSN
- 2005-6419
- eISSN
- 2005-7563
- Publisher
- Korean Soc Anesthesiologists
- Number of pages
- 12
- Grant note
- 2017R1A2B4004803 / National Research Foundation of Korea (NRF) - Ministry of Science and ICT; National Research Foundation of Korea; Ministry of Science, ICT & Future Planning, Republic of Korea
- Language
- English
- Date published
- 08/01/2024
- Academic Unit
- Anesthesia
- Record Identifier
- 9984806510602771
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