Molecular targets of neuroplasticity in ischemic stroke: insights from GEO database, single-cell analysis and immune infiltration analysis.

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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.", "claims": [{"id": "claim-method", "statement": "To identify DEGs in mouse brain samples from MCAO and control mice in the GSE61616 datasets, we conducted differential expression analysis using the “limma” package (Alhussaini et al., 2024). After batch correction, we established |log2 fold change (FC)| > 1 and adjusted p-value < 0.05 as the thresholds.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40787669", "locator": "sections[4] \"Identification of differentially expressed genes (DEGs)\" paragraph 2", "quote": "To identify DEGs in mouse brain samples from MCAO and control mice in the GSE61616 datasets, we conducted differential expression analysis using the “limma” package (Alhussaini et al., 2024). After batch correction, we established |log2 fold change (FC)| > 1 and adjusted p-value < 0.05 as the thresholds."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40787669", "locator": "sections[25] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Differential expression analysis of GSE61616 identified 2,046 DEGs, including 1,533 upregulated and 513 downregulated genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40787669", "locator": "sections[14] \"Identification of DEGs\" paragraph 2", "quote": "The analysis of DEGs (GSE61616) was performed using the “limma” package, obtaining 2046 DEGs (1,533 up-regulated and 513 downregulated)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Differential expression analysis of GSE61616 identified 2,046 DEGs, including 1,533 upregulated and 513 downregulated genes.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40787669"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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