Alarmin HMGB1 Plays a Detrimental Role in Hippocampal Dysfunction Caused by Hypoxia-Ischemia Insult in Neonatal Mice: Evidence from the Application of the HMGB1 Inhibitor Glycyrrhizin.,ACS Chemical Neuroscience

当前位置： X-MOL 学术 › ACS Chem. Neurosci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Alarmin HMGB1 Plays a Detrimental Role in Hippocampal Dysfunction Caused by Hypoxia-Ischemia Insult in Neonatal Mice: Evidence from the Application of the HMGB1 Inhibitor Glycyrrhizin.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-03-02 , DOI: 10.1021/acschemneuro.0c00084
Kai Le _{1,

2} , Shanshan Wu _{1,

2} , Enkhmurun Chibaatar _{1,

2} , Abdoulaye Idriss Ali _{1,

2} , Yijing Guo ₁

Affiliation

Hippocampal dysfunction related to cognitive impairment and emotional disorders in young children and adolescents caused by neonatal hypoxic-ischemic brain injury (HIBI) has attracted increasing attention in recent years. Crosstalk between the nervous and immune systems organized by hypoxia-ischemia (HI) insult may contribute to hippocampal dysfunction after HIBI. Extracellular HMGB1 functions as a damage-associated molecular pattern to instigate and amplify inflammatory responses, but whether this molecule is correlated with hippocampal dysfunction after HIBI is largely unknown. Therefore, this study examined hippocampal function after HMGB1 inhibition in an experimental HIBI model to verify the hypothesis that HMGB1 is a key mediator of hippocampal neuropathology in neonatal HIBI. By administering different doses of the HMGB1-specific inhibitor glycyrrhizin (GLY), we first found that GLY reversed the HI insult-induced loss of neurons and myelin in the hippocampal region and neurobehavioral impairments, partially in a dose-dependent manner, and based on this, we determined the optimal drug concentration to be 50 mg/kg. Subsequent analysis found that this neuroprotective effect was achieved through the inhibition of HMGB1 expression and nucleocytoplasmic translocation, a reduction in the abnormal expression of proteins associated with the downstream signaling pathway of HMGB1, a decrease in the inflammatory response, the suppression of increases in microglia/astrocytes, and the inhibition of hippocampal cell apoptosis. Collectively, our discoveries contribute to the rising appreciation of the role of HMGB1 in the neuropathology of hippocampal dysfunction and related behavioral outcomes following HIBI.

中文翻译：

Alarmin HMGB1在新生鼠体内缺氧缺血性损伤引起的海马功能障碍中起有害作用：来自HMGB1抑制剂甘草甜素应用的证据。

新生儿缺氧缺血性脑损伤（HIBI）引起的与年幼儿童和青少年的认知障碍和情绪障碍相关的海马功能障碍已引起越来越多的关注。缺氧缺血（HI）损伤组织的神经系统和免疫系统之间的串扰可能导致HIBI后海马功能障碍。细胞外HMGB1作为损伤相关分子模式来激发和放大炎症反应，但是在HIBI后该分子是否与海马功能障碍相关尚不清楚。因此，本研究在实验性HIBI模型中检查了HMGB1抑制后的海马功能，以验证HMGB1是新生儿HIBI的海马神经病理学关键介质的假设。通过施用不同剂量的HMGB1特异性抑制剂甘草甜素（GLY），我们首先发现GLY可以部分依赖剂量依赖性地逆转HI损伤诱导的海马区神经元和髓磷脂的丧失以及神经行为受损，这是基于剂量依赖性的为此，我们确定最佳药物浓度为50 mg / kg。随后的分析发现，这种神经保护作用是通过抑制HMGB1的表达和核质易位，减少与HMGB1下游信号通路相关的蛋白质的异常表达，降低炎症反应，抑制小胶质细胞/星形胶质细胞，并抑制海马细胞凋亡。总的来说，

更新日期：2020-03-03

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11