Abstract: An enriched environment is used as a behavioral intervention therapy that applies sensory, motor, and social stimulation, and has been used in basic and clinical research of various neurological diseases. In this study, we established mouse models of photothrombotic stroke and, 24 hours later, raised them in a standard, enriched, or isolated environment for 4 weeks. Compared with the mice raised in a standard environment, the cognitive function of mice raised in an enriched environment was better and the pathological damage in the hippocampal CA1 region was remarkably alleviated. Furthermore, protein expression levels of tumor necrosis factor receptor-associated factor 6, nuclear factor κB p65, interleukin-6, and tumor necrosis factor α, and the mRNA expression level of tumor necrosis factor receptor-associated factor 6 were greatly lower, while the expression level of miR-146a-5p was higher. Compared with the mice raised in a standard environment, changes in these indices in mice raised in an isolated environment were opposite to mice raised in an enriched environment. These findings suggest that different living environments affect the hippocampal inflammatory response and cognitive function in a mouse model of stroke. An enriched environment can improve cognitive function following stroke through up-regulation of miR-146a-5p expression and a reduction in the inflammatory response.

Key words: cognitive function, enriched environment, isolated environment, miR-146a-5p, neuroinflammation, nuclear factor κB p65, photothrombotic model, stroke, tumor necrosis factor receptor-associated factor 6