Propofol Protects the Blood-Brain Barrier After Traumatic Brain Injury by Stabilizing the Extracellular Matrix via Prrx1: From Neuroglioma to Neurotrauma

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemical Research Pub Date : 2024-07-01 DOI:10.1007/s11064-024-04202-z
Lan Zhang, Chenrui Wu, Tao Liu, Yu Tian, Dong Wang, Bo Wang, Yiqing Yin
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Abstract

The purpose of this study is to explore the shared molecular pathogenesis of traumatic brain injury (TBI) and high-grade glioma and investigate the mechanism of propofol (PF) as a potential protective agent. By analyzing the Chinese glioma genome atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases, we compared the transcriptomic data of high-grade glioma and TBI patients to identify common pathological mechanisms. Through bioinformatics analysis, in vitro experiments and in vivo TBI model, we investigated the regulatory effect of PF on extracellular matrix (ECM)-related genes through Prrx1 under oxidative stress. The impact of PF on BBB integrity under oxidative stress was investigated using a dual-layer BBB model, and we explored the protective effect of PF on tight junction proteins and ECM-related genes in mice after TBI. The study found that high-grade glioma and TBI share ECM instability as an important molecular pathological mechanism. PF stabilizes the ECM and protects the BBB by directly binding to Prrx1 or indirectly regulating Prrx1 through miRNAs. In addition, PF reduces intracellular calcium ions and ROS levels under oxidative stress, thereby preserving BBB integrity. In a TBI mouse model, PF protected BBB integrity through up-regulated tight junction proteins and stabilized the expression of ECM-related genes. Our study reveals the shared molecular pathogenesis between TBI and glioblastoma and demonstrate the potential of PF as a protective agent of BBB. This provides new targets and approaches for the development of novel neurotrauma therapeutic drugs.

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丙泊酚通过 Prrx1 稳定细胞外基质保护创伤性脑损伤后的血脑屏障:从神经胶质瘤到神经创伤。
本研究旨在探索创伤性脑损伤(TBI)和高级别胶质瘤的共同分子发病机制,并研究丙泊酚(PF)作为一种潜在保护剂的机制。通过分析中国胶质瘤基因组图谱(CGGA)和癌症基因组图谱(TCGA)数据库,我们比较了高级别胶质瘤和创伤性脑损伤患者的转录组数据,以确定共同的病理机制。通过生物信息学分析、体外实验和体内 TBI 模型,我们研究了 PF 在氧化应激下通过 Prrx1 对细胞外基质(ECM)相关基因的调控作用。我们利用双层 BBB 模型研究了 PF 在氧化应激下对 BBB 完整性的影响,并探讨了 PF 对小鼠 TBI 后紧密连接蛋白和 ECM 相关基因的保护作用。研究发现,高级别胶质瘤和创伤性脑损伤共同的重要分子病理机制是 ECM 不稳定。PF 可直接与 Prrx1 结合或通过 miRNA 间接调节 Prrx1,从而稳定 ECM 并保护 BBB。此外,PF 还能降低氧化应激下的细胞内钙离子和 ROS 水平,从而保护 BBB 的完整性。在创伤性脑损伤小鼠模型中,PF 通过上调紧密连接蛋白和稳定 ECM 相关基因的表达来保护 BBB 的完整性。我们的研究揭示了创伤性脑损伤和胶质母细胞瘤之间共同的分子发病机制,并证明了 PF 作为 BBB 保护剂的潜力。这为开发新型神经创伤治疗药物提供了新的靶点和方法。
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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
期刊介绍: Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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