HMGB1 and brain ischemia: Recent studies highlight HMGB1 as a key mediator of the crosstalk between NETosis and thrombosis: during the acute phase of cerebral ischemia, HMGB1 expression on platelets is significantly upregulated, mediating platelet aggregation, activation, and thrombosis via the TLR4/MyD88 and cGMP/PKG pathways.74, 75Activated platelets release HMGB1, it subsequently attaches to neutrophils' TLR4 and receptor for advanced glycation end products (RAGE), causing NETosis and encouraging thrombus development.67, 75, 76, 77