38 THE FUNCTION AND MECHANISM OF EXTRACELLULAR VESICLES IN POSTOPERATIVE COGNITIVE DYSFUNCTION

Abstract

Background Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients, showing a decline in memory, attention and executive function, which affects the quality of life and recovery. Exosomes, as mediators of cell-cell communication, have attracted much attention in neurological diseases, which contain a variety of bioactive molecules that can participate in the CNS regulation through the blood-brain barrier. Currently, the function and mechanism of exosomes in POCD remain unclear. The study will explore the role of exosome in POCD through animal experiments and molecular biology techniques, and provide new targets for clinical intervention. Methods Healthy adult male C57BL/6 mice weighing 20-25g were divided into Sham group (n=20), POCD group (n=30), and POCD intervention group (n=30). The POCD model was constructed by common carotid artery ligation and isoflurane anesthesia. Spatial learning and memory abilities were assessed on postoperative days 1,3, and 7 using the Morris water maze (MWM). After the experiment, the distribution in the brain of fluorescently labeled exosomes was visualized by tail vein injection, and the expression of miRNA and key proteins in the exosomes was analyzed by Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and proteomics techniques. The Western blot and immunofluorescence labeling techniques were used to verify the relationship between molecules and neuroinflammation in exosomes. Data were analyzed using the SPSS 26.0 software, and the differences between groups were compared by one-way analysis of variance (ANOVA). Results Comparison of the main indicators between the groups is shown in Table 1. Table 1 shows that mice in the POCD group had prolonged latency on postoperative days 1 and 3, shorter residence time in the target quadrant, and improved cognitive function in the intervention group. After exosome tail vein injection, the fluorescence signal was enhanced in the hippocampus, indicating that exosomes penetrate the blood-brain barrier. By RT-qPCR, inflammation-related miRNA expression was up-regulated in exosomes in the POCD group, with the expression decreased after intervention. Proteomic analysis showed that the expression of proteins related to IL-6, TNF- α, and NF- κ B signaling pathway was increased in exosomes in the POCD group, and decreased after intervention. Immunofluorescence showed that the proportion of Iba-1-positive microglia activation in the hippocampus of the POCD group was high and decreased after the intervention. Discussion The function and mechanism of exosomes in POCD were systematically investigated. The results indicate that exosomes can enter the CNS through the blood-brain barrier and affect neuroinflammation and cognitive function recovery in the hippocampus by regulating inflammation-related miRNA and protein expression. This provides new molecular targets and theoretical ale for POCD intervention. Future studies should further validate the specific downstream signaling pathways of miRNA in exosomes in POCD, optimize the intervention methods, and explore its potential in clinical applications.