Background
Developing effective approaches for postoperative delirium has been hampered due to the lack of a pathophysiologically similar animal model to offer insights into the pathogenesis. The study, therefore, aimed to develop a delirium-like mouse model and explore the underlying mechanism.
Conclusion
The repeated intestinal I/R surgery-induced mouse model is a simple and reproducible one of postoperative delirium. Peripheral IL-6-associated microglial QUIN elevations in the BLA contributed to cognitive dysfunction in the model of postoperative delirium.
Methods
The three cycles of 10-min clamp following 5-min reopening of the superior mesenteric artery (SMA) were performed in adult male C57BL/6 mice to induce a delirium-like phenotype. Composite Z score calculated based on the
Results
The repeated ischemia/reperfusion (I/R) surgery caused significant anxiety (P < 0.05) and cognition decline in working memory and orientation (P < 0.05) in mice at postoperative 24 h. The composite Z score, indicating an overall disturbance of brain function, fluctuated over 24 h after I/R surgery (P < 0.001). Immunofluorescent staining showed that the percentage of microglia in the basolateral amygdala (BLA) (P < 0.05) was reactivated after I/R surgery and was negatively correlated with dwell time at Y maze (R = -0.759, P = 0.035). Inhibiting microglia activities by MINO reduced QUIN productions (P < 0.01) that improved cognitive deficits (P < 0.05). The peripheral IL-6 might cause IL-6 elevation in the BLA. Systemic administration of IL-6 antibodies suppressed I/R-induced IL-6 elevations (P < 0.05), microglial reactivations (P < 0.05), IDO-1 expressions (P < 0.01), and neuroactive metabolite QUIN productions (P < 0.05) in the BLA, resulting in a recovery of cognitive deficits (P < 0.05). Injection of IL-6 exerted opposite effects.