AUTHOR=Zhao Boyan , Wu Jianing , Han Mingyang , Rong Xuan , Jin Jin , Liu Shiya , Zhang Cheng , Zhang Ruotian , Chen Xin , Peng Fei , Dong Xingli , Zhao Shiguang 

TITLE=Exosome-related genes influence the progression of stroke through neuroinflammatory responses

JOURNAL=Frontiers in Neurology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1517588

DOI=10.3389/fneur.2025.1517588

ISSN=1664-2295

ABSTRACT=Ischemic stroke (IS) ranks among the top causes of mortality and disability globally. Exosomes exert a crucial effect on maintaining a complex regulatory balance with neuroinflammation in IS. Hence, this research aimed to elucidate the roles of exosome-related genes IS. We integrated data from five IS-related datasets from the Gene Expression Omnibus (GEO) database and exosome-related genes from ExoCarta. The least absolute shrinkage and selection operator regression and random forest models were performed to detect feature genes. Search Tool for the Retrieval of Interacting Genes and Cytoscape were employed to recognize the hub genes. Enrichment analyses were conducted to examine biological processes. CIBERSORT and MCPcounter were applied to assess immune infiltration, and Principal Component Analysis was utilized to explore the associations of feature genes and hub genes with immune cells. After identified different cell types, we analyzed differentiation, developmental trajectory, and interactions of the cell populations. Middle cerebral artery occlusion models were conducted on mice, followed by quantitative polymerase chain reaction to assess the expression levels of each hub gene. We identified 13 feature genes and 10 hub genes. Through qPCR, LGALS3, CD36, TLR2, ICAM1, and CD14 were significantly upregulated after Middle Cerebral Artery Occlusion surgery. Hub genes were significantly involved in inflammatory responses, as well as chemokine signaling and JAK–STAT signaling. Immuno-infiltration analysis revealed significant differences in immune cell populations between IS and controls. Additionally, neutrophils and monocytes/macrophages were positively correlated with CD14 and LGALS3, respectively. Single-cell analysis revealed 19 cell subpopulations with detailed pseudo-time trajectory predictions, highlighting the developmental importance of MG2 microglial cells. In conclusion, our results illuminate exosomal genes, including LGALS3 and CD14, participate in the progression of IS through neuroinflammation, as well as highlight potential therapeutics to mitigate IS injury.