{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T14:14:19Z","timestamp":1779804859084,"version":"3.53.1"},"reference-count":64,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2024110042"],"award-info":[{"award-number":["H2024110042"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The aim of this study is to investigate the precise mechanisms by which Polydatin (PD) ameliorates cerebral ischemia\u2013reperfusion injury (CIRI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We first established a rat model of CIRI to evaluate PD's therapeutic effects. Transcriptomic analysis was used to explore PD's impact on gene expression in ischemic brain tissue of CIRI rats. OGD\/R\u2010induced microglial activation experiments validated that PD inhibits microglial activation by targeting the CXCL3\/CXCR2 axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PD intervention improved neurological function scores of CIRI rats, reduced infarct area, alleviated pathological damage, and preserved Nissl bodies in brain tissue. It also modulated oxidative stress levels. Transcriptomic analysis showed enrichment of the Cytokine\u2013cytokine receptor interaction pathway and several inflammatory pathways after PD intervention, with downregulation of CXCL3 and CXCR2. PD decreased pro\u2010inflammatory cytokine levels and CXCL3\/CXCR2 protein expression in ischemic brain tissue of CIRI rats, and reduced positive expression areas of IBA1\n                      <jats:sup>+<\/jats:sup>\n                      CXCL3\n                      <jats:sup>+<\/jats:sup>\n                      , IBA1\n                      <jats:sup>+<\/jats:sup>\n                      CXCR2\n                      <jats:sup>+<\/jats:sup>\n                      , and MPO\n                      <jats:sup>+<\/jats:sup>\n                      CXCR2\n                      <jats:sup>+<\/jats:sup>\n                      . In\u00a0vitro experiments demonstrated that PD reduced pro\u2010inflammatory cytokine levels in BV2 cell supernatants treated with OGD\/R and inhibited BV2 cell migration. However, these effects were abolished when treated with CXCL3 neutralizing antibody and SiCXCR2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that PD can inhibit microglial migration and activation by acting on the CXCL3\/CXCR2 axis, thereby alleviating the inflammatory response in CIRI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70947","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T09:41:14Z","timestamp":1779529274000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polydatin Inhibits Neuroinflammation in Cerebral Ischemia\u2013Reperfusion Injury Through Suppressing the\n                    <scp>CXCL3<\/scp>\n                    \/\n                    <scp>CXCR2<\/scp>\n                    Axis"],"prefix":"10.1002","volume":"32","author":[{"given":"Youxiang","family":"Cui","sequence":"first","affiliation":[{"name":"Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine  Cangzhou China"},{"name":"Key Laboratory of Neurological Rehabilitation Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine  Cangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangmei","family":"Hu","sequence":"additional","affiliation":[{"name":"Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine  Cangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixin","family":"Wang","sequence":"additional","affiliation":[{"name":"Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine  Cangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehua","family":"Liu","sequence":"additional","affiliation":[{"name":"Qingxian 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