Late Anxiety-Like Behavior and Neuroinflammation in Mice Subjected to Sublethal Polymicrobial Sepsis

Sepsis can lead to long-term cognitive changes, including memory and learning deficits, which are known as septic encephalopathy (SE). SE also includes behavioral changes. The underlying mechanism of SE is unknown, and several mechanisms have been proposed. This study investigated late anxiety-like behavior, serum cytokine levels and brain cytokine production in C57BL/6 mice subjected to polymicrobial sepsis induced by sublethal cecum ligature and puncture (CLP). Anxiety-like behavior and locomotor activity were assessed in mice 10 days after sham operation or CLP procedure using the elevated plus maze, contextual fear conditioning, and open field test. Brain and serum concentrations of the cytokines TNF-alpha, IFN-gamma, IL-1 beta, IL-6, and IL-10 were determined by ELISA. We found that mice subjected to polymicrobial sepsis presented anxiety-like behavior, which was accompanied by increased serum TNF-alpha and brain TNF-alpha, IFN-gamma, IL-1 beta, and IL-6 levels, 10 days after the surgical procedure. These findings suggest an involvement of central nervous system inflammatory mediators in the anxiety-like symptoms found in SE.