Gou Xiaoyun, Ying Junjie, Yue Yan, Qiu Xia, Hu Peng, Qu Yi, Li Jinhui, Mu Dezhi
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects, Ministry of Education, Sichuan University, Chengdu, China.
Front Cell Neurosci. 2020 Dec 15;14:600280. doi: 10.3389/fncel.2020.600280. eCollection 2020.
High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that plays an important role in stabilizing nucleosomes and DNA repair. HMGB1 can be passively released from necrotic neurons or actively secreted by microglia, macrophages/monocytes, and neutrophils. Cerebral ischemia is a major cause of mortality and disability worldwide, and its outcome depends on the number of neurons dying due to hypoxia in the ischemic area. HMGB1 contributes to the pathogenesis of cerebral ischemia via mediating neuroinflammatory responses to cerebral ischemic injury. Extracellular HMGB1 regulates many neuroinflammatory events by interacting with its different cell surface receptors, such as receptors for advanced glycation end products, toll-like receptor (TLR)-2, and TLR-4. Additionally, HMGB1 can be redox-modified, thus exerting specific cellular functions in the ischemic brain and has different roles in the acute and late stages of cerebral ischemic injury. However, the role of HMGB1 in cerebral ischemia is complex and remains unclear. Herein, we summarize and review the research on HMGB1 in cerebral ischemia, focusing especially on the role of HMGB1 in hypoxic ischemia in the immature brain and in white matter ischemic injury. We also outline the possible mechanisms of HMGB1 in cerebral ischemia and the main strategies to inhibit HMGB1 pertaining to its potential as a novel critical molecular target in cerebral ischemic injury.
高迁移率族蛋白B1（HMGB1）是一种普遍存在的核蛋白，在稳定核小体和DNA修复中发挥重要作用。HMGB1可从坏死神经元中被动释放，或由小胶质细胞、巨噬细胞/单核细胞和中性粒细胞主动分泌。脑缺血是全球范围内导致死亡和残疾的主要原因，其后果取决于缺血区域因缺氧而死亡的神经元数量。HMGB1通过介导对脑缺血损伤的神经炎症反应，促进脑缺血的发病机制。细胞外HMGB1通过与其不同的细胞表面受体相互作用来调节许多神经炎症事件，如晚期糖基化终产物受体、Toll样受体（TLR）-2和TLR-4。此外，HMGB1可进行氧化还原修饰，从而在缺血性脑中发挥特定的细胞功能，并在脑缺血损伤的急性期和晚期发挥不同作用。然而，HMGB1在脑缺血中的作用复杂且仍不清楚。在此，我们总结并综述了关于HMGB1在脑缺血中的研究，特别关注HMGB1在未成熟脑缺氧缺血和白质缺血损伤中的作用。我们还概述了HMGB1在脑缺血中的可能机制以及抑制HMGB1的主要策略，涉及其作为脑缺血损伤新型关键分子靶点的潜力。
