The high mobility group box-1 protein (HMGB1), as a nuclear DNA-binding protein and an important damage associated molecular pattern (DAMP), is released from necrotic and dying neural cells in the ischemic brain, leading to the activation of microglia and the expression of inflammatory factors in ischemic brain, and it may activate TLR 2/4 and RAGEs signaling following rapid translocation to the cytoplasm or release from dying cells after cerebral ischemia [9,10], which can promote the activation of inflammatory responses. The gene discussed is HMGB1; the disease is brain ischemia.