Neurogenesis after traumatic brain injury - The complex role of HMGB1 and neuroinflammation

Traumatic brain injury (TBI) is amongst the leading causes of morbidity and mortality worldwide. Despite evidence neurogenesis post-TBI, survival integration newborn neurons remains impaired. High Mobility Group Box protein 1 (HMGB1) an ‘alarmin’ released hyper-acutely following TBI implicated in hosting neuro-inflammatory response to injury. It also instrumental mediating under physiological conditions. Given its dual role neuro-inflammation neurogenesis, it serves as a promising putative target for therapeutic modulation. In this review, we discuss neuro-pharmacological aspects HMGB1, potential target. PubMed database was searched with varying combinations search terms: isoforms, traumatic injury, Toll-like receptor (TLR), advanced glycation end-products (RAGE). Several vitro vivo studies demonstrate post-injury. The HMGB1-RAGE axis mediates throughout development, whilst interaction TLR-4 promotes innate immune response. Studies context that these effects are not mutually exclusive. recognition different HMGB1 isoforms based on redox/acetylation status, post-injury remain unexplored. Recent animal examining antagonism post-TBI predominantly positive results, but specific longer-term outcomes unclear. failure several pharmacological strategies improve TBI, accurate delineation signalling pathways vital.