Department of Neurosurgery, Southampton General Hospital, Southampton, UK.
Neuroscience and Mental Health Research Institute (NMHRI), School of Medicine, Cardiff University, UK.
Neuropharmacology. 2021 Feb 1;183:108400. doi: 10.1016/j.neuropharm.2020.108400. Epub 2020 Nov 13.
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.
外伤性脑损伤（TBI）是全球发病率和死亡率的主要原因之一。尽管有证据表明 TBI 后存在神经发生，但新生神经元的存活和整合仍受到损害。高迁移率族蛋白 B1（HMGB1）是 TBI 后超急性释放的“警报素”，并与损伤后的神经炎症反应有关。它在生理条件下介导神经发生中也起着重要作用。鉴于其在介导神经炎症和神经发生中的双重作用，它是治疗调节的有前途的潜在靶标。在这篇综述中，我们讨论了 TBI 后的神经发生、HMGB1 的神经药理学方面及其作为治疗靶标的潜力。
使用以下搜索词的不同组合在 PubMed 数据库中进行搜索：HMGB1、同种型、神经发生、外伤性脑损伤、Toll 样受体（TLR）、晚期糖基化终产物受体（RAGE）。
几项体外和体内研究表明损伤后存在神经发生的证据。HMGB1-RAGE 轴介导整个发育过程中的神经发生，而与 TLR-4 的相互作用促进先天免疫反应。在损伤背景下的研究表明，这些受体作用并非相互排斥。尽管根据氧化还原/乙酰化状态识别了不同的 HMGB1 同种型，但损伤后对神经发生的影响仍未得到探索。最近的动物体内研究表明，TBI 后检查 HMGB1 拮抗作用主要产生积极结果，但对神经发生和长期结果的具体影响仍不清楚。
HMGB1 是一个有前途的治疗靶标，但它对 TBI 后神经发生的影响仍不清楚。鉴于几种药理学策略未能改善 TBI 后的结果，因此准确描绘 HMGB1 信号通路及其对损伤后神经发生的影响至关重要。
