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• W3102887918 endingPage "108400" @default.
• W3102887918 startingPage "108400" @default.
• W3102887918 abstract "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. 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). 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. 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." @default.
• W3102887918 created "2020-11-23" @default.
• W3102887918 creator A5016882601 @default.
• W3102887918 creator A5035099982 @default.
• W3102887918 creator A5062208871 @default.
• W3102887918 creator A5062590640 @default.
• W3102887918 date "2021-02-01" @default.
• W3102887918 modified "2023-09-23" @default.
• W3102887918 title "Neurogenesis after traumatic brain injury - The complex role of HMGB1 and neuroinflammation" @default.
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