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Metabolomic profiling reveals persistent metabolic alterations and selective working memory deficits following neonatal anesthesia in rats

Year: 2026

Type: article

Abstract: Preclinical studies have established that common pediatric anesthetics such as sevoflurane and propofol can induce neurotoxicity, yet their molecular mechanisms remain incompletely elucidated. This study combined LC-MS-based metabolomics with caspase-3 and cleaved caspase-3 immunoblotting, Y-maze, and Morris water maze testing to investigate metabolic alterations linked to anesthesia-induced neurotoxicity in neonatal Sprague-Dawley rats. Animals at postnatal day 7 (P7) were exposed to a single 2-hour session of sevoflurane or propofol anesthesia and assessed at 6 h (P7) and 35 days (P42) post-exposure. Both anesthetics significantly upregulated hippocampal caspase-3 and cleaved caspase-3 expression at both time points and resulted in long-term decline of working memory in the Y-maze test at P42. However, no significant cognitive alteration was detected in the Morris water maze test at P42. Metabolomic analysis revealed anesthetic-specific metabolic disturbances in the hippocampus. In propofol-treated rats, six metabolites—indole, isoleucine, lysine, phenylalanine, D-ribose 5-phosphate, and biotin—were consistently and significantly elevated at 6 h and 35 days post-anesthesia. All six metabolites showed a strong positive correlation with caspase-3 levels. In contrast, sevoflurane anesthesia led to a marked and sustained downregulation of phosphatidylcholine PC (16:0/16:0), which correlated negatively with caspase-3 expression. This study identifies distinct hippocampal metabolite profiles associated with prolonged neurotoxicity induced by propofol and sevoflurane. The propofol-related metabolites—indole, isoleucine, lysine, phenylalanine, D-ribose 5-phosphate, and biotin—and the sevoflurane-associated metabolite PC (16:0/16:0) represent potential intervention targets for mitigating the adverse neurodevelopmental effects of general anesthesia in neonates.

Source: Scientific Reports

DOI: 10.1038/s41598-026-69987-1

Authors: Xingqu Chen, Li Yang, Ling Qiu, Deshui Yu, Xiaobin Wang

Institutions: Southwest Medical University, Affiliated Hospital of Southwest Medical University, Second People’s Hospital of Yibin

Language: English

Topic: Anesthesia and Neurotoxicity Research

Subfield: Developmental Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690