VASP、HCLS1、MSN 和 EZR:脑出血后血肿周围水肿病理生理学中的关键分子信标

IF 1.3 Q4 CLINICAL NEUROLOGY Brain Hemorrhages Pub Date : 2024-10-01 DOI:10.1016/j.hest.2024.04.002
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引用次数: 0

摘要

目的血脑屏障水肿(PHE)是严重的继发性脑损伤之一,血脑屏障的完整性在其发展过程中起着关键作用。加强紧密连接(TJ)蛋白可提高血脑屏障的完整性,但脑水肿背后复杂的遗传学机制仍未完全明了。我们的研究致力于发现脑出血后脑水肿的关键基因及其在脑水肿中的作用,并研究潜在的治疗策略。方法通过使用 GSE216607 和 GSE206971 数据集分析脑出血(ICH)和对照样本,我们确定了差异表达的基因。通过与 KEGG 数据库交叉比对,我们将这些基因与紧密连接相关基因进行了比对。我们还进行了广泛的富集分析和蛋白质相互作用分析,以检验所发现基因的表达和临床意义。我们的研究采用了 C57BL/6J 小鼠 ICH 模型和 qRT-PCR 方法对关键基因进行验证。药物验证表明,庚酸睾酮、SELENIUM和LY 294002对紧密连接相关基因具有潜在的治疗作用。需要进一步研究以加深理解。
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VASP, HCLS1, MSN, and EZR: Key molecular beacons in the pathophysiology of perihematomal edema Post-Intracerebral hemorrhage

Objective

Perihematomal edema (PHE) is one of the significant secondary cerebral damages, with the blood–brain barrier's integrity playing a pivotal role in its progression. Strengthening tight junction (TJ) proteins enhances blood–brain barrier integrity, yet the complex genetics behind brain edema remain not fully understood. Our research endeavors to uncover pivotal genes and their roles in brain edema following cerebral hemorrhage, and to investigate potential treatment strategies.

Methods

By analyzing intracerebral hemorrhage (ICH) and control samples using the GSE216607 and GSE206971 datasets, we identified differentially expressed genes. Cross-referencing with the KEGG database, we aligned these genes with those related to tight junctions. Extensive enrichment analysis and protein interactions were performed to examine the expression and clinical significance of the identified genes. Our study employed the C57BL/6J mouse ICH model and qRT-PCR for key gene validation.

Results

Notably, VASP, HCLS1, MSN, and EZR, critical for tight junctions, showed increased expression post-ICH, emphasizing their significance in BBB upkeep and PHE progression. Drug validation indicated potential therapeutic effects of Testosterone enanthate, SELENIUM, and LY 294002 on tight junction-related genes.

Conclusion

This study sheds light on the potential involvement of these genes in brain edema progression post-ICH, offering promising therapeutic targets. Further research is needed for deeper understanding.
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来源期刊
Brain Hemorrhages
Brain Hemorrhages Medicine-Surgery
CiteScore
2.90
自引率
0.00%
发文量
52
审稿时长
22 days
期刊最新文献
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