TLR4 and ischemic stroke: Furthermore, TLR4-mediated signaling pathways activate the downstream targets JNK and p38 mitogen-activated protein kinase (MAPK), which in turn induce TLR4 upregulation, amplifying TLR4/NF-κB-mediated signaling and exacerbating infarct expansion in the acute stage of ischemic stroke (Cheng et al., 2021; Dong et al., 2021).