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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.<\/jats:p>","DOI":"10.1038\/s41598-026-66143-7","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:44:33Z","timestamp":1787373873000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Recombinant CXCL16 reduces brain injury by modulating microglial phenotype and attenuating apoptosis in acute ischemic stroke"],"prefix":"10.1038","volume":"16","author":[{"given":"Hongyi","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengfei","family":"Luan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taoli","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"66143_CR1","doi-asserted-by":"crossref","unstructured":"Zhou, Y. et al. 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