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Background Traumatic brain injuries (TBI) are associated with complex inflammatory pathways that lead to the development of secondary injuries such as cerebral ischemia, elevated intracranial pressure, and cognitive deficits. The association between intracellular danger signaling involving nuclear chromatin-binding factor, high mobility group box-1 (HMGB1), and inflammatory pathways following TBI has not yet been fully understood. Primary Objective To comprehensively review the available literature regarding the potential diagnostic, prognostic and therapeutic use of HMGB1 in TBI. Methods A systematic literature review of studies available in PubMed using human and animal subjects was performed. A total of eight studies were included in our results. Conclusions Comprehensive review of these reports demonstrated that following TBI, HMGB1 is released from damaged neurons and is elevated in patient’s serum and CSF. Furthermore, these studies showed the potential for HMGB1 to serve as a prognostic biomarker and therapeutic target in patients with TBI. Thus, HMGB1 is a prospective candidate for future studies as it shows promise in treating and/or predicting the sequelae of TBI.

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