A Murine Model of Pseudomonas aeruginosa Pneumonia-Induced Sepsis-Associated Encephalopathy Reveals Upregulation of the NLRP3/Caspase-1/IL-1β Pathway

Objective: This study first established a murine model of pneumonia-induced sepsis-associated encephalopathy (SAE) via intranasal administration of Pseudomonas aeruginosa (PA), aiming to provide a complementary model that more closely mimics the clinical course of pneumonia-derived sepsis, and explored the role of the NLRP3/caspase-1/IL-1β pathway in this model. Methods: Mice were intranasally given PAO1 to induce pulmonary infection-derived SAE, with intraperitoneal lipopolysaccharide (LPS) as a positive control and sham operation as a control. SAE was verified by clinical assessment and histopathology 24 h post-intervention. Hippocampal NLRP3, ASC and caspase-1 were detected by RT-qPCR; serum IL-1β, IL-18, TNF-α, S100B, neuron-specific enolase (NSE) and NT-proCNP were measured by ELISA. Results: Intranasal instillation of 1.2 × 107 CFU PAO1 successfully replicated SAE in mice. Hippocampal mRNA levels of NLRP3, ASC, caspase-1, as well as serum concentrations of the above inflammatory and brain injury markers, were significantly higher in the SAE and LPS groups than in the sham group (all p < 0.05). No significant temporal differences in those serum indicators were observed at 8, 16 and 24 h among groups (all p > 0.05). Conclusions: We successfully established a PA pneumonia-induced murine SAE model. Using this model, we demonstrated that upregulation of the NLRP3/caspase-1/IL-1β signaling pathway is associated with the pathogenesis and progression of SAE.