Liesz et al. (2015) reported that HMGB1 is released at the acute stage of ischemia from the injured brain in both the mice model and patients, and HMGB1-RAGE signaling participates in the ischemic stroke, which was believed to be critical for clarifying the mechanism of the brain–immune interaction after ischemia. Here, HMGB1 is linked to ischemic stroke.