Zhang Dong, Jing Xinying, Ma Ruinan, Li Zhizhang, Zhang Xiaoguang, Ding Ying, Yue Yunhua
Department of Neurology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China.
Front Neurosci. 2025 Aug 14;19:1581758. doi: 10.3389/fnins.2025.1581758. eCollection 2025.
Acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) is a leading cause of disability and mortality worldwide. Although endovascular thrombectomy (EVT) has significantly improved outcomes, many patients do not achieve early neurological improvement (ENI) despite timely reperfusion. This study aims to investigate the peripheral blood mRNA molecular characteristics and underlying mechanisms associated with ENI after EVT in AIS-LVO patients, to inform individualized treatment and optimize prognosis.
This retrospective study included AIS-LVO patients who underwent EVT between January 2022 and December 2023. Peripheral blood samples were collected before reperfusion therapy for mRNA transcriptome sequencing and bioinformatic analysis. Patients were grouped according to ENI status. Differentially expressed genes (DEGs) were identified, and functional enrichment, signaling pathway, and protein-protein interaction network analyses were performed.
A total of 108 patients were initially screened, and 20 were ultimately included in the study (13 in the ENI group and 7 in the non-ENI group). Among the 20,501 genes detected, 752 were found to be significantly differentially expressed, with 208 upregulated and 544 downregulated. The upregulated genes in the ENI group were mainly enriched in immune and inflammatory response pathways, such as NOD-like receptor and Toll-like receptor signaling. In contrast, the downregulated genes were primarily associated with neurodevelopment and synaptic plasticity. Protein-protein interaction analysis identified immune-related genes, including JUN, IL1A, and CCR5, as central nodes. Overall, the ENI group exhibited a dynamic balance between immune activation and suppression of neuronal plasticity.
This study reveals the transcriptomic characteristics of ENI in AIS-LVO patients during the acute phase, highlighting the protective roles of moderate immune-inflammatory activation and suppression of neural plasticity in acute injury response. The identification of related molecular pathways and biomarkers provides a theoretical basis for individualized treatment and improved functional outcomes. Future studies should expand sample size and integrate single-cell sequencing and liquid biopsy multi-omics approaches to further clarify the molecular mechanisms of ENI and promote clinical translation.
由大血管闭塞（LVO）引起的急性缺血性卒中（AIS）是全球范围内导致残疾和死亡的主要原因。尽管血管内血栓切除术（EVT）显著改善了治疗结果，但许多患者尽管实现了及时再灌注，却未实现早期神经功能改善（ENI）。本研究旨在调查AIS-LVO患者接受EVT后与ENI相关的外周血mRNA分子特征及潜在机制，为个体化治疗和优化预后提供依据。
这项回顾性研究纳入了2022年1月至2023年12月期间接受EVT的AIS-LVO患者。在再灌注治疗前采集外周血样本进行mRNA转录组测序和生物信息学分析。根据ENI状态对患者进行分组。鉴定差异表达基因（DEG），并进行功能富集、信号通路和蛋白质-蛋白质相互作用网络分析。
最初筛选出108例患者，最终20例纳入研究（ENI组13例，非ENI组7例）。在检测到的20,501个基因中，发现752个基因有显著差异表达，其中208个上调，544个下调。ENI组上调的基因主要富集于免疫和炎症反应途径，如NOD样受体和Toll样受体信号通路。相比之下，下调的基因主要与神经发育和突触可塑性相关。蛋白质-蛋白质相互作用分析确定免疫相关基因，包括JUN、IL1A和CCR5，为中心节点。总体而言，ENI组在免疫激活和神经元可塑性抑制之间表现出动态平衡。
本研究揭示了急性期AIS-LVO患者ENI的转录组特征，突出了适度免疫炎症激活和神经可塑性抑制在急性损伤反应中的保护作用。相关分子途径和生物标志物的鉴定为个体化治疗和改善功能结局提供了理论基础。未来的研究应扩大样本量，并整合单细胞测序和液体活检多组学方法，以进一步阐明ENI的分子机制并促进临床转化。
