OBJECTIVE: This study investigated whether repeated Sev exposure induces cognitive impairment in developing rats and examined the involvement of gut-derived inflammatory mediators.
METHODS: Thirty postnatal Sprague-Dawley rats were randomly assigned to five groups: control, sevoflurane (Sev), sevoflurane control (Sev-Con), antibiotic-treated (ANT), and sevoflurane plus antibiotic-treated (Sev+ANT). Cognitive performance was assessed using the Morris water maze, while inflammatory markers, barrier-related proteins, microbial metabolites, and gut microbiota composition were analyzed using western blotting, immunohistochemistry, gas chromatography, and 16S rRNA gene sequencing.
RESULTS: Rats in the Sev group exhibited significant impairments in spatial learning and memory compared with controls. Sev exposure increased serum and hippocampal levels of lipopolysaccharide (LPS), trimethylamine N-oxide (TMAO), and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), while reducing the expression of the tight junction protein ZO-1 in colonic and hippocampal tissues. In addition, protein levels of TLR4, phosphorylated NF-κB p65, and NLRP3 were elevated in the hippocampus. Antibiotic pretreatment attenuated these alterations. No significant differences in short-chain fatty acid (SCFA) levels were observed following sevoflurane exposure. 16S rRNA gene sequencing revealed sevoflurane-associated shifts in gut microbiota composition at the genus level, characterized by increased relative abundances of Ligilactobacillus, Faecousia, and Alloprevotella and a decreased abundance of Lactobacillus.
CONCLUSION: Repeated sevoflurane exposure during development was associated with cognitive impairment and alterations in gut microbiota-related inflammatory signaling along the gut-brain axis. Broad-spectrum antibiotic pretreatment attenuated these changes, suggesting that gut microbiota-related processes may contribute to sevoflurane-associated neurocognitive dysfunction, although causal inference remains limited because antibiotics may exert microbiota-independent effects.
Gut-Brain Axis