{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:01:30Z","timestamp":1784178090756,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,13]],"date-time":"2025-07-13T00:00:00Z","timestamp":1752364800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["PL2024H104"],"award-info":[{"award-number":["PL2024H104"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ischemic stroke, a leading cause of global morbidity and disability, involves incompletely elucidated pathophysiological mechanisms. Emerging evidence highlights pyroptosis\u2014an inflammatory programmed cell death pathway\u2014as a critical contributor to ischemic brain injury progression. The pro\u2010inflammatory mediator S100a9 may exacerbate neuronal damage through pyroptosis regulation, prompting this investigation into its role in post\u2010stroke outcomes and underlying mechanisms. We employed a multi\u2010modal approach integrating public omics datasets, clinical cohorts, murine middle cerebral artery occlusion (MCAO) models, and cellular oxygen\u2013glucose deprivation\/reperfusion (OGD\/R) systems to delineate expression patterns of S100a9 and pyroptosis\u2010associated biomarkers. Pharmacological targeting of S100a9 using Paquinimod and siRNA\u2010mediated knockdown further defined its functional regulation of pyroptotic cascades. Results demonstrate that S100a9 amplifies neuroinflammatory responses and microglia\u2010specific pyroptosis, correlating with worsened infarct volumes and poor 30\u2010day modified Rankin Scale scores. Targeted S100a9 inhibition attenuated brain injury and neuroinflammation, highlighting its potential as a therapeutic target for stroke intervention.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70159-fig-0008-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70159","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T06:39:26Z","timestamp":1752475166000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["S100a9 Aggravates Ischemia Brain Injury via Pyroptosis Pathway: A Potential Prognostic Biomarker and Therapeutic Target for Ischemic Stroke"],"prefix":"10.1111","volume":"169","author":[{"given":"Wenchao","family":"Fu","sequence":"first","affiliation":[{"name":"The Heilongjiang Key Laboratory of Anesthesia and Intensive Care Research, Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"The Heilongjiang Key Laboratory of Anesthesia and Intensive Care Research, Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Xu","sequence":"additional","affiliation":[{"name":"The Heilongjiang Key Laboratory of Anesthesia and Intensive Care Research, Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Heilongjiang Key Laboratory of Anesthesia and Intensive Care Research, Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[{"name":"The Heilongjiang Key Laboratory of Anesthesia and Intensive Care Research, Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Shen","sequence":"additional","affiliation":[{"name":"The Heilongjiang Key Laboratory of Anesthesia and Intensive Care Research, Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinfei","family":"Song","sequence":"additional","affiliation":[{"name":"The Heilongjiang Key Laboratory of Anesthesia and Intensive Care Research, Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingbo","family":"Li","sequence":"additional","affiliation":[{"name":"The Heilongjiang Key Laboratory of Anesthesia and Intensive Care Research, Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University Harbin Medical University  Harbin Heilongjiang 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