Exploring OLR1-mediated inflammatory mechanisms in the hematoma microenvironment of acute intracerebral hemorrhage

IF 2.8 3区 医学 Q2 NEUROSCIENCES Neuroscience Pub Date : 2025-05-07 Epub Date: 2025-03-18 DOI:10.1016/j.neuroscience.2025.03.035
Zhilu Sun , Likun Wang , Siying Ren , Long Wang , Guofeng Wu
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Abstract

Intracerebral hemorrhage (ICH) is a devastating form of stroke with high mortality and limited therapeutic options. The current study investigates the role of oxidative low-density lipoprotein receptor 1 (OLR1) within the hematoma microenvironment, focusing on its impact on immune responses and disease progression in ICH patients. Through comprehensive bioinformatics analyses of datasets from the Gene Expression Omnibus (GEO), including peripheral blood, brain tissue, and hematoma samples, we identified significant upregulation of OLR1, particularly in hematoma regions. This upregulation was strongly correlated with increased monocyte and macrophage activity, exacerbating neuroinflammation and contributing to poor clinical outcomes. Single-cell RNA sequencing (scRNA-seq) further elucidated the involvement of OLR1 in monocyte-driven immune responses, suggesting its critical role in the pathophysiology of ICH. Validation through quantitative real-time PCR (qRT-PCR) confirmed that OLR1 expression was significantly higher in hematoma samples than in peripheral blood, with the most notable elevation observed in patients with poor prognoses. Our findings suggest that OLR1 could serve as a promising biomarker and therapeutic target for modulating immune responses in ICH. Targeted therapies to regulate OLR1 expression could potentially mitigate neuroinflammation and improve recovery outcomes. This study not only enhances the understanding of the molecular mechanisms underlying ICH but also provides a foundation for developing novel therapeutic strategies that focus on the hematoma microenvironment and immune modulation.
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探索急性脑内出血血肿微环境中 OLR1 介导的炎症机制。
脑出血(ICH)是一种毁灭性的中风形式,死亡率高,治疗选择有限。目前的研究探讨了氧化性低密度脂蛋白受体1 (OLR1)在血肿微环境中的作用,重点关注其对脑出血患者免疫反应和疾病进展的影响。通过对基因表达综合(GEO)数据集(包括外周血、脑组织和血肿样本)的综合生物信息学分析,我们发现OLR1显著上调,特别是在血肿区域。这种上调与单核细胞和巨噬细胞活性的增加密切相关,从而加剧神经炎症并导致不良的临床结果。单细胞RNA测序(scRNA-seq)进一步阐明了OLR1参与单核细胞驱动的免疫应答,提示其在脑出血病理生理中起关键作用。通过实时荧光定量PCR (qRT-PCR)验证,血肿样本中的OLR1表达明显高于外周血,在预后较差的患者中表达最为显著。我们的研究结果表明,OLR1可以作为一种有希望的生物标志物和治疗靶点来调节脑出血的免疫反应。调节OLR1表达的靶向治疗可能潜在地减轻神经炎症并改善恢复结果。本研究不仅增强了对脑出血分子机制的理解,而且为开发新的血肿微环境和免疫调节治疗策略提供了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Neuroscience
Neuroscience 医学-神经科学
CiteScore
6.20
自引率
0.00%
发文量
394
审稿时长
52 days
期刊介绍: Neuroscience publishes papers describing the results of original research on any aspect of the scientific study of the nervous system. Any paper, however short, will be considered for publication provided that it reports significant, new and carefully confirmed findings with full experimental details.
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