Energy intake restriction significantly improves POCD after internal fixation of tibial fractures in mice

Objective: To investigate the effect of energy intake restriction on postoperative cognitive dysfunction (POCD) after internal fixation of tibial fractures in mice. Methods: Thirty mice were divided into model groups of internal fixation of tibial fractures with 0%, 20%, 30% and 40% energy intake restriction and sham operation group (n = 6). Novel object recognition task and elevated plus maze test were used to assess the ability of recognition memory and anxiety-related behavior before and one week after surgery. The blood samples were collected from mice on days 1, 3 and 7 after surgery, and the mice were euthanized on the 8th day after surgery. RT-PCR and Western blot were employed to detect the expression of AMPK-SIRT1 pathway-related genes and proteins in the hippocampus. ELISA was used to detect the levels of inflammatory factors in the peripheral blood of mice. Hematoxylin-eosin (H&E) staining and immunofluorescence (IF) staining were used to detect the proliferation, differentiation and injury of hippocampal cells. Results: The results showed that 20% and 30% energy intake restriction significantly improved the POCD after internal fixation of tibial fractures in mice. Significantly, 30% energy intake restriction reduced the expression of AP-1, NF-κB, CD45, IBA-1, and inflammatory factors IL-1β, IL-6, IL-8 and TNF-α, and increased the expression of AMPK and SIRT1 after the operation. H&E and IF staining showed that 30% energy intake restriction reduced postoperative hippocampal neuronal damage. Conclusion: Energy intake restriction can significantly improve POCD after internal fixation of tibial fractures in mice and may provide a new treatment paradigm for POCD patients.