Across numerous animal models and in vitro studies, ω-3 PUFAs and RvD1 (Resolvin D1), a specific pro-resolving mediator that is synthesized from ω-3 PUFAs, particularly EPA, consistently demonstrate a significant reduction in HMGB1 [44,46,125,155,158,159,161,163,164,165], S100β [160], and NSE [156,162] levels in response to diverse conditions like TBI, ischemia-reperfusion injury, cognitive decline, and inflammatory diseases. Here, HMGB1 is linked to ischemia reperfusion injury.