AGER and Stroke: In stroke, HMGB-1 acts as a pro-inflammatory cytokine that activates microglia through the receptor of advanced glycation end-product (RAGE) and TLR-MyD88 pathways, producing immunosuppressive and lymphotoxic effects that further aggravate brain injury (Liesz et al., 2015; Jayaraj et al., 2019).