Sevoflurane exposure in early life: mitochondrial dysfunction and neurotoxicity in immature rat brains without long-term memory loss.

Autor: Qiu L; Department of Anesthesia, Henan Provincial People's Hospital, Department of Anesthesia of Central China Fuwai Hospital, Central China Fu Wai Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, China. qiulin2005@163.com.; Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, 450003, China. qiulin2005@163.com., Li H; Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.; Department of Laboratory Medicine, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.; Zhengzhou Key Laboratory for In Vitro Diagnosis of Hypertensive Disorders of Pregnancy, Zhengzhou, 450052, China., Li B; Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China., Ek J; Perinatal Center, Department of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, 40530, Sweden., Zhang X; Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China., Chen Y; Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China., Shao Z; Department of Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China., Zhang J; Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China., Zhang J; Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, 450003, China., Lin H; Department of Anesthesia, Henan Provincial People's Hospital, Department of Anesthesia of Central China Fuwai Hospital, Central China Fu Wai Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, China.; Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, 450003, China., Zhu C; Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.; Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, 40530, Sweden., Xu Y; Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. yiran.xu@zzuneuro.cn., Wang X; Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. xiaoyang.wang@fysiologi.gu.se.; Perinatal Center, Department of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, 40530, Sweden. xiaoyang.wang@fysiologi.gu.se.; Centre of Perinatal Medicine & Health, Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 41685, Sweden. xiaoyang.wang@fysiologi.gu.se.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Nov 20; Vol. 14 (1), pp. 28747. Date of Electronic Publication: 2024 Nov 20.
DOI: 10.1038/s41598-024-79150-3
Abstrakt: 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.
Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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