BRIEF RESEARCH REPORT article
Front. Aging Neurosci.
Sec. Cellular and Molecular Mechanisms of Brain-aging
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1561282
Molecular Targets of Neuroplasticity in Ischemic Stroke: Insights from GEO Database, Single-cell Analysis and Immune Infiltration Analysis
Provisionally accepted
- 1Hebei Normal University, Shijiazhuang, Hebei Province, China
- 2Third Hospital of Hebei Medical University, Shijiazhuang, China
- 3Key Laboratory of Measurement and Evaluation in Exercise Bioinformation of Hebei Province, Shijiazhuang, China
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This study is aimed to identify diagnostic and therapeutic biomarkers related to neuroplasticity in IS. Gene expression profiling (GSE61616) was derived from GEO, and neuroplasticity-related genes were obtained from the GeneCards databases. The overlapping genes related to neuroplasticity were processed for GO and KEGG analysis.The protein interaction network and hub genes were identified using Cytoscape and the PPI network. Then we predicted the potential TFs and miRNAs related to hub genes. Single-cell analysis was performed to explore cellular localization and intercellular communications related to hub genes in GSE167593. Immune infiltration characteristics were explored via GSVA package. The correlation between various immune cells and hub genes (CCR5 and CXCR4) was calculated via linKET package. Finally, DGIdb database was used for screening small-molecule drugs of CCR5 and CXCR4. Our study screened five significant neuroplasticity-related hub genes (CCR5, CXCR4, TIMP1, GRIN1 and GRM1). Moreover, single-cell analysis revealed that the CCR5 was specifically expressed in microglia and macrophages, while the CXCR4 was specifically expressed in T cells, NK cells, macrophages, and granulocytes. Immune infiltration and correlation analysis revealed a positive association of CCR5 with aDCs and T helper cells, while CXCR4 was positively correlated with CD8+ T cells, but negatively correlated with Tfh. Finally, the Leronlimab, Ulocuplumab, Burixafor, and MSX-122 are promising drugs to treat IS via targeting on CCR5 and CXCR4. In conclusion, our findings suggest that CCR5 and CXCR4 are promising targets for enhancing neuroplasticity post-ischemic stroke, thus providing potentially effective and reliable therapeutic targets for future interventional strategy.
Keywords: ischemic stroke, GEO analysis, Single cells analysis, immune infiltration analysis, Neuroplasticity-related genes
Received: 15 Jan 2025; Accepted: 08 Jul 2025.
Copyright: © 2025 Yang, Li, Zhang, Zhang, Liu, Chen and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Feng Zhang, Third Hospital of Hebei Medical University, Shijiazhuang, China
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