Mice subjected to tibial fracture surgery exhibited neuroinflammation and cognitive impairment due to TLR4/MyD88 signaling-mediated upregulation of S100A8 in the peripheral blood mononuclear cells (PBMCs), spleen, and hippocampus; however, microgliosis was reduced in both TLR4-deficient and MyD88-deficient mice and anxiety/cognitive dysfunction was reversed in TLR4-deficient mice [71]. Here, TLR4 is linked to Anxiety.