Sevoflurane exposure in early life: mitochondrial dysfunction and neurotoxicity in immature rat brains without long-term memory loss
Neurotoxic effects of general anesthetics, particularly sevoflurane, on pediatric neurodevelopment are a global concern. This study investigated the molecular and metabolic impacts of repeated short exposures to sevoflurane in neonatal rats. Metabolomics analysis revealed significant changes in fatty acid and mitochondrial energy metabolism. Transcriptomic analysis identified altered gene expression related to neurodevelopment and mitochondrial function. Various analyses emphasized upregulation in oxidative phosphorylation and DNA repair pathways. Weighted gene co-expression network analysis (WGCNA) identified key gene modules associated with sevoflurane exposure. Despite these acute changes, no significant long-term memory impairments were detected. These findings highlight the impact of sevoflurane on mitochondrial energy metabolism, oxidative stress, and neuroinflammation, emphasizing its relevance to pediatric neurodevelopment. The absence of substantial long-term memory impairments provides insights into the safety and implications of sevoflurane use in pediatric anesthesia, calling for further research.
Authors
- C. Joakim Ek (ORCID: https://orcid.org/0000-0002-5764-7679)
- Zehua Shao
- Hongqi Lin (ORCID: https://orcid.org/0000-0002-6711-4200)
- Yiran Xu (ORCID: https://orcid.org/0000-0002-9004-0377)
- Hongwei Li (ORCID: https://orcid.org/0000-0001-6809-7097)
- Xiaoyang Wang (ORCID: https://orcid.org/0000-0001-9717-8160)
- Bingbing Li (ORCID: https://orcid.org/0000-0003-0531-4335)
- Xiaoli Zhang (ORCID: https://orcid.org/0000-0001-8837-8558)
- Jie Zhang (ORCID: https://orcid.org/0000-0001-6795-8000)
- Yiwen Chen (ORCID: https://orcid.org/0000-0003-3480-8262)
- Jiaqiang Zhang (ORCID: https://orcid.org/0000-0002-4165-0312)
- Lin Qiu (ORCID: https://orcid.org/0000-0002-6813-1598)
- Changlian Zhu (ORCID: https://orcid.org/0000-0002-5029-6730)
Institutions
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Zhengzhou University (CN)
- Henan Provincial People's Hospital (CN)
- Zhengzhou Central Hospital (CN)
- Third Affiliated Hospital of Zhengzhou University (CN)
- Fu Wai Hospital (CN)
- University of Gothenburg (SE)
Publication Details
- Journal
- Scientific Reports
- Published
- 2024-11-20
- DOI
- https://doi.org/10.1038/s41598-024-79150-3
- Citations
- 7
- Primary Topic
- Anesthesia and Neurotoxicity Research
- Type
- article
- Field-Weighted Citation Impact
- 2.88
Funders
- National Natural Science Foundation of China
- Vetenskapsrådet
- Göteborgs Universitet
- Science and Technology Department of Henan Province