Journal Article

Study on the Mechanism of Eerdun Wurile’s Effects on Post-operative Cognitive Dysfunction by the TLR4/NF-κB Pathway

Wang, Zhe, Che, Limuge, Su, Enboer, Li, Yan, Du, Yiri, Li, Huiru, Qiao, Yun

2023

Overview

The object of our work was to observe whether the Mongolian medicine Eerdun Wurile (EW) improve postoperative cognitive dysfunction (POCD) by affecting the TLR4/NF-κB. Mice (6–8-week-old male C57BL/6 J) were selected to establish an animal model of POCD by combining intracerebroventricular injection of lipopolysaccharide and nephrectomy; EW formulation and EW basic formulation were administered intra-gastrically for 7 consecutive days. The cognitive performance was assessed by Morris water maze test. H&E staining was examined to detect alterations in hippocampal tissue. Immunohistochemical staining was performed to evaluate MyD88, NF-κB, TLR4, iNOS, and IBA-1 expressions; Western blotting and RT-qPCR were performed to evaluate MyD88, NF-κB, and TLR4. The expressions of IL-6, IL-1β, and TNF-α were evaluated by ELISA. Intracerebroventricular injection of lipopolysaccharide combined with nephrectomy induced cognitive dysfunction in mice, stimulated TLR4/NF-κB and microglia, and promoted the secretion of murine TNF-α, IL-1β, and IL-6. EW formulation and EW basic formulation treatment are able to suppress the TLR4/NF-κB pathway activation and microglia, and the serum cytokine secretions related to proinflammation, and restore the cognitive performance. EW formulation and EW basic formulation can improve POCD in mice, and TLR4/NF-κB pathway seems to be one of the important mechanisms in EW’s improvement of POCD.

• Publisher: Springer US,Springer Nature B.V
• Subject: Animal cognition / Animal models / Animals / Biomedical and Life Sciences / Biomedicine / Cell Biology / Cognitive ability / Cognitive Dysfunction / Cytokines / Enzyme-linked immunosorbent assay / Hippocampus / IL-1β / Inflammation / Interleukin 6 / Ligands / Lipopolysaccharides / Lipopolysaccharides - pharmacology / Male / Medical research / Medicine / Memory / Mice / Mice, Inbred C57BL / Microglia / MyD88 protein / Myeloid Differentiation Factor 88 / Nephrectomy / Nervous system / Neurobiology / Neurological disorders / Neurology / Neurosciences / NF-kappa B / NF-κB protein / Nitric-oxide synthase / Postoperative Cognitive Complications / Secretions / Surgery / TLR4 protein / Toll-Like Receptor 4 / Toll-like receptors / Trauma / Tumor Necrosis Factor-alpha / Tumor necrosis factor-α / Western blotting