Research Paper Volume 14, Issue 6 pp 2590—2606

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

Wei Zhang1, , Ruohan Wang2, , Jingli Yuan2, , Bing Li1, , Luyao Zhang1, , Yangyang Wang1, , Ruilou Zhu1, , Jiaqiang Zhang1, *, , Ting Huyan3, *, ,

  • 1 Department of Anesthesiology and Perioperative Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China
  • 2 Department of Anesthesiology and Perioperative Medicine, Henan University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
  • 3 Key Laboratory for Space Biosciences and Biotechnology, Institute of Special Environment Biophysics, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, Shaanxi Province, China
* Equal contribution

Received: December 28, 2021       Accepted: February 15, 2022       Published: March 16, 2022
How to Cite

Copyright: © 2022 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


POD: Postoperative delirium; Non-POD: Non-delirium; POCD: Postoperative cognition dysfunction; MAGI-2: Membrane-associated guanylate kinase-2; TLR4: Toll-like receptor 4; NF-κB: Nuclear factor-κB; PDTC: Pyrrolidine dithiocarbamate.