Recombinant CXCL16 reduces brain injury by modulating microglial phenotype and attenuating apoptosis in acute ischemic stroke.

Overview

1. Center for Neurological Function Test and Neuromodulation, West China Hospital, West China Xiamen Hospital, Sichuan University, 699 Jinyuan West Road, Xingbin Street, Jimei District, Xiamen, 361000 China
2. Department of Critical Care Medicine (ICU), The First People’s Hospital of Yibin, No. 65 Wenxing Street, Cuiping District, Yibin, 644000 Sichuan China
3. Department of Clinical Psychology, Zhongshan Third People’s Hospital, 80 Tianbian Zheng Street, Nanlang Town, Zhongshan, 528400 China
4. Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin China
5. Department of Neurology, University of Giessen, Giessen, Germany
6. Department of Neurology, West China School of Medicine, Sichuan University, Sichuan University affiliated Chengdu Second People’s Hospital, Chengdu Second People’s Hospital, Chengdu, 610017 Sichuan China

Abstract

Chemokines are traditionally known for their roles in immune cell recruitment during inflammation, but emerging evidence suggests that they may also directly regulate cellular states within the central nervous system. Specifically, it remains unclear whether CXCL16 affects microglial functional states in ischemic stroke. Here, we demonstrated that recombinant CXCL16 (rCXCL16) modulated the expression of inflammation- and repair-associated markers in primary microglia and in the ischemic brain. Functionally, microglia pretreated with rCXCL16 increased HT-22 cell viability and reduced apoptosis in an indirect co-culture system. Consistently, in vivo administration of rCXCL16 reduced infarct size, restored neurobehavior performance, and suppressed apoptosis in experimental stroke in mice. These findings identify rCXCL16 as a modulator of microglial responses and suggest that its neuroprotective effects are associated with reduced inflammatory marker expression and attenuation of apoptotic injury after ischemic stroke.

Supplementary Information: The online version contains supplementary material available at 10.1038/s41598-026-66143-7.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE227651, at NCBI GEO; found in “Data availability”

Data availability

Data are available from the corresponding author on request. The single-cell RNA-sequencing data analyzed in this study are publicly available in the Gene Expression Omnibus under accession number GSE227651 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE227651).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 7 keywords, 12 MeSH terms, 1 funder, 29 references.

Cite

This paper

Sun, H., Zhou, C., Hu, J., Luan, T., & Lu, T. (2026). Recombinant CXCL16 reduces brain injury by modulating microglial phenotype and attenuating apoptosis in acute ischemic stroke. Scientific reports, 16(1), 26358. https://doi.org/10.1038/s41598-026-66143-7

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