The Role of HMGB1 in Traumatic Brain Injury—Bridging the Gap Between the Laboratory and Clinical Studies

Traumatic brain injury (TBI) is amongst the leading causes of mortality and morbidity worldwide. However, several pharmacological strategies in the clinical setting remain unsuccessful. Mounting evidence implicates High Mobility Group Box protein 1 (HMGB1) as a unique alternative target following brain injury. Herein, we discuss current understanding of HMGB1 in TBI and obstacles to clinical translation.HMGB1 plays a pivotal role as a 'master-switch' of neuro-inflammation following injury and in the regulation of neurogenesis during normal development. Animal models point towards the involvement of HMGB1 signalling in prolonged activation of glial cells and widespread neuronal death. Early experimental studies demonstrate positive effects of HMGB1 antagonism on both immunohistochemical and neuro-behavioural parameters following injury. Raised serum/CSF HMGB1 in humans is associated with poor outcomes post-TBI. HMGB1 is a promising therapeutic target post-TBI. However, further studies elucidating receptor, cell, isoform, and temporal effects are required prior to clinical translation.