Traumatic brain injury (TBI) can cause brain cell death/dying, and the/dead/dying cells can release nuclear protein HMGB1 that can activate inflammatory pathways, therefore, the HMGB1 inhibitor EP (75 mg/kg was intraperitoneally injected at 5 min, 1 h, 6 h after brain injury, and brain samples were harvested 24 h after brain injury) significantly decreases the expressions of HMGB1, TLR4, NF-kB DNA binding and inflammatory mediators, such as, TNF-α, IL-1 and IL-6. Here, HMGB1 is linked to injury.