{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T16:25:51Z","timestamp":1761582351294,"version":"build-2065373602"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cerebral ischemic stroke remains a leading cause of mortality and morbidity worldwide. Toll\u2010like receptor 4 (TLR4) has been implicated in neuroinflammatory responses poststroke, particularly in the infiltration of immune cells and polarization of macrophages. This study aimed to elucidate the impact of TLR4 deficiency on neutrophil infiltration and subsequent macrophage polarization after middle cerebral artery occlusion (MCAO), exploring its role in stroke prognosis. The objective was to investigate how TLR4 deficiency influences neutrophil behavior poststroke, its role in macrophage polarization, and its impact on stroke prognosis using murine models. Wild\u2010type and TLR4\u2010deficient adult male mice underwent MCAO induction, followed by various analyses, including flow cytometry to assess immune cell populations, bone marrow transplantation experiments to evaluate TLR4\u2010deficient neutrophil behaviors, and enzyme\u2010linked immunosorbent assay and Western blot analysis for cytokine and protein expression profiling. Neurobehavioral tests and infarct volume analysis were performed to assess the functional and anatomical prognosis poststroke. TLR4\u2010deficient mice exhibited reduced infarct volumes, increased neutrophil infiltration, and reduced M1\u2010type macrophage polarization post\u2010MCAO compared to wild\u2010type mice. Moreover, the depletion of neutrophils reversed the neuroprotective effects observed in TLR4\u2010deficient mice, suggesting the involvement of neutrophils in mediating TLR4's protective role. Additionally, N1\u2010type neutrophils were found to promote M1 macrophage polarization via neutrophil gelatinase\u2010associated lipocalin (NGAL) secretion, a process blocked by TLR4 deficiency. The study underscores the protective role of TLR4 deficiency in ischemic stroke, delineating its association with increased N2\u2010type neutrophil infiltration, diminished M1 macrophage polarization, and reduced neuroinflammatory responses. Understanding the interplay between TLR4, neutrophils, and macrophages sheds light on potential therapeutic targets for stroke management, highlighting TLR4 as a promising avenue for intervention in stroke\u2010associated neuroinflammation and tissue damage.<\/jats:p>","DOI":"10.1002\/cbf.4059","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T02:45:26Z","timestamp":1716345926000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Improving stroke prognosis by TLR4 KO to enhance N2 neutrophil infiltration and reduce M1 macrophage polarization"],"prefix":"10.1002","volume":"42","author":[{"given":"Fuhong","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Neurology Affiliated Hospital of Chifeng University Chifeng Inner Mongolia 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