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

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

A diagnostic dilemma in Jordan: two child abuse case studies.

Child abuse was diagnosed in two Jordanian children. The first was a 15-month-old female infant admitted with a history of convulsions and loss of consciousness. The child had previous head and limb injuries resulting in bilateral subdural hematomas and fractures at different stages of healing of femur and pelvis. The second was a 3-year-old male admitted with history of head injury due to an alleged fall. Examination revealed fractured ribs, bruised eye and face, hemothorax, subperiosteal and subdural hematomas. Both children have sustained physical and mental handicaps. This is the first report of child abuse in Jordan. In Jordan, as in the rest of the world, a high index of suspicion is needed to diagnose child abuse early enough to save the affected child its serious sequelae.