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

Mol Neurobiol. 2023 Dec;60(12):7274-7284. doi: 10.1007/s12035-023-03537-y. Epub 2023 Aug 7.

Abstract

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.

Keywords: Eerdun Wurile (EW) in Mongolian medicine; Lipopolysaccharide (LPS); Post-operative cognitive dysfunction (POCD); TLR4/NF-κB pathway.

MeSH terms

  • Animals
  • Cognitive Dysfunction*
  • Interleukin-6
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Postoperative Cognitive Complications*
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha

Substances

  • NF-kappa B
  • Toll-Like Receptor 4
  • Interleukin-6
  • Lipopolysaccharides
  • Myeloid Differentiation Factor 88
  • Tumor Necrosis Factor-alpha