The TLR4/NF-κB/MAGI-2 signaling pathway mediates postoperative delirium

Purpose: To evaluate the TLR4/NF-κB/MAGI-2 signaling pathway in postoperative delirium. Methods: Elderly patients aged 65-80 years who received unilateral hip arthroplasty under subarachnoid anesthesia were included. Pre-anesthesia cerebrospinal fluid and perioperative blood samples were collected. After follow-up, patients were divided into two groups according to the occurrence of postoperative delirium (POD) after surgery. The potential differentially expressed proteins in the two groups were determined by proteomics assay and subsequent western blot validation. A POD model of aged mice was established, and the TLR4/NF-κB/MAGI-2 signaling pathway was determined. Main findings: The IL-1β and TNF-α levels in pre-anesthesia cerebrospinal fluid and postoperative blood were higher in patients who developed POD than in those patients who did not. Compared with non-POD patients, MAGI-2 was highly expressed in POD patients, as validated by proteomics assays and western blotting. Higher p-NF-κB-p65, TLR4 and MAGI-2 in POD patients were detected by western blot. The POD model in aged mice was successfully established and verified by three behavioral tests. Postoperative inflammatory cytokines and the TLR4/NF-κB/MAGI-2 signaling pathway were increased in mice with POD. Inhibiting TLR4/NF-κB/MAGI-2 signaling pathway could reduce postoperative delirium. Conclusions: The TLR4/NF-κB/MAGI-2 signaling pathway mediates POD.