Introduction

Sepsis-associated encephalopathy (SAE) is a severe complication of sepsis, characterized by neuroinflammation and cognitive dysfunction, with high morbidity and mortality. This study investigated the therapeutic potential of fibroblast growth factor-18 (FGF-18) for alleviating SAE using a mouse model.

Material and methods

We employed immunohistochemistry, ELISA, Western blot, real-time polymerase chain reaction (RT-PCR), and the Morris water maze test to evaluate the effects of FGF-18 overexpression.

Results

The results demonstrated that FGF-18 expression was significantly reduced in the brain cortex of SAE mice. Overexpression of FGF-18 alleviates cognitive impairment, reduces neuroinflammation, and suppresses the activation of microglia and astrocytes. Mechanistically, FGF-18 inhibits the nuclear factor -light-chain-enhancer of activated B cells (NF-B) and JNK/STAT3 pathways in microglia and the NFAT5/AQP-4 axis in astrocytes, both of which are critical in SAE pathogenesis. Specifically, FGF-18 reduces cerebral levels of pro-inflammatory cytokines (tumor necrosis factor  [TNF-], interleukin [IL]-6, and IL-1) and decreases the expression of the microglial marker Iba-1 and the astrocytic marker GFAP, indicating reduced activation of these cells.

Conclusions

These findings suggest that FGF-18 may serve as a promising therapeutic target for SAE by modulating neuroinflammatory responses and improving cognitive outcomes. The study highlights the potential of FGF-18 to mitigate the neuroinflammatory cascade in SAE, offering a novel strategy to improve clinical outcomes for sepsis patients. Further in vitro studies are warranted to validate these mechanisms and explore translational applications. This research underscores the importance of targeting microglia and astrocyte activation in the treatment of SAE, providing new insights into the role of FGF-18 in neuroinflammation and cognitive dysfunction.