Environmental conditions differentially affect neurobehavioral outcomes in a mouse model of sepsis-associated encephalopathy

Abstract

Brain dysfunction remains a common complication after sepsis development and is an independent risk factor for a poorer prognosis and an increased mortality. Here we tested the hypothesis that the behavioral outcomes after lipopolysaccharides (LPS) administration are exacerbated by an impoverished environment (IE) and alleviated by an enriched environment (EE), respectively. Mice were randomly allocated in a standard environment (SE), an EE, or an IE for 4 weeks after LPS or normal saline (NS) administration. Neurobehavioral alternations were assessed by the open field, novel objective recognition, and fear conditioning tests. The expressions of proinflammatory cytokines (tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10), ionized calcium-binding adaptor molecule-1 (IBA1)-positive cells as well as glial fibrillary acidic protein (GFAP)-positive cells, brain derived neurotrophic factor (BDNF), 5-bromo-2-deoxyuridine-labeled cells in the dentate gyrus of the hippocampus, and the number of dendritic spines in the hippocampal CA1 were determined. Our results showed that the some of the neurocognitive abnormalities induced by LPS administration can be aggravated by stressful conditions such as IE but alleviated by EE. These neurocognitive alternations were accompanied by significant changes in biomarkers of immune response and hippocampal synaptic plasticity. In summary, our study confirmed the negative impact of IE and the positive effects of EE on the cognitive function after LPS administration, with potential implications to the basis of sepsis-related cognitive impairments in the critically ill patients.