513 Understanding the Role of HMGB1 Post-Traumatic Brain Injury - The Complex Interplay Between Neuro-Inflammation and Neurogenesis

Traumatic brain injury (TBI) is a global public health burden. Although neurogenesis occurs post-injury, achieving long term survival of newly generated neurons remains elusive. High Mobility Group Box protein 1 (HMGB1) is a pivotal cytokine in hosting the neuro-inflammatory response to injury, but also mediates neurogenesis during physiological development. In this review, we examine current evidence for post-traumatic neurogenesis and HMGB1 as a therapeutic target. Method PubMed database was evaluated with the following search terms: HMGB1, isoforms, neurogenesis, traumatic brain injury, Toll-like receptor, receptor for advanced glycation end-products. Results Multiple studies support the existence of neurogenesis post-injury both in vitro and in vivo. Different HMGB1 target receptors mediate different functions of HMGB1, though these are not mutually exclusive in the context of injury. Interaction with RAGE is responsible for developmental neurogenesis, whilst TLR-4 mediates the innate immune response. Though different HMGB1 isoforms are recognised, specific effects post-injury remains unexplored. In vivo animal studies demonstrate positive effects of HMGB1 antagonism post-TBI, but long-term outcomes remain unclear. Conclusions Modulating HMGB1 may enhance post-TBI recovery, but a mechanistic understanding of its effects on neurogenesis is fundamental to avoid negating potentially beneficial effects.