HMGB1 and ischemic stroke: Ischemic stroke leads to extensive HMGB1 release from dying neurons in the infarct core starting within 30 min of onset, followed by a delayed second wave of active HMGB1 secretion from reactive astrocytes and microglia that can persist for weeks (Hayakawa, Qiu & Lo, 2010; Chen et al., 2019).