At the early phase of stroke, HMBG1 mediates ischemia–reperfusion injury by activating microglia through TLR-4 signaling, such as increased NF-kB activity, NO production, transcriptional upregulation of COX-2 (cyclooxygenase2), TNF-a and IL-1β [38]. Here, NFKB1 is linked to stroke disorder.