{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T19:07:37Z","timestamp":1788808057129,"version":"build-2803163510"},"reference-count":77,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Serum amyloid A (SAA) proteins increase significantly in the blood following inflammation. Recently, SAAs were increased in humans following stroke and in ischemic animal models. However, the impact of SAAs on whether this signal is critical in the ischemic brain remains unknown. Therefore, we investigated the role of SAA and SAA signaling in the ischemic brain. Wild-type and SAA-deficient mice were exposed to middle cerebral artery occlusion and reperfusion and examined to determine the impact of infarct volumes, behavioral changes, inflammatory markers, TUNEL staining, and BBB changes. The underlying mechanisms were investigated using SAA-deficient mice, transgenic mice, and viral vectors. SAA levels were significantly increased following MCAo, and mice deficient in SAA showed reduced infarct volumes and improved behavioral outcomes. SAA-deficient mice showed a reduction in TUNEL staining, inflammation, and decreased glial activation. Mice lacking acute phase SAAs demonstrated a reduction in the expression of the NLRP3 inflammasome, and SAA\/NLRP3 KO mice showed improvement. The restoration of SAA expression via SAA tg mice or adenoviral expression re-established the detrimental effects of SAA. A reduction in BBB permeability was seen in SAA KO mice, and anti-SAA antibody treatment reduced the effects on ischemic injury. SAA signaling plays a critical role in regulating NLRP3-induced inflammation and glial activation in the ischemic brain. Blocking this signal will be a promising approach for treating ischemic stroke.<\/jats:p>","DOI":"10.3390\/ijms27052281","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T10:24:34Z","timestamp":1772447074000},"page":"2281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Serum Amyloid A-Dependent Inflammasome Activation and Acute Injury in a Mouse Model of Experimental Stroke"],"prefix":"10.3390","volume":"27","author":[{"given":"Jin","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeid","family":"Taheri","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June-Yong","family":"Lee","sequence":"additional","affiliation":[{"name":"The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4155-8687","authenticated-orcid":false,"given":"David M.","family":"Diamond","sequence":"additional","affiliation":[{"name":"Department of Psychology, College of Arts and Sciences, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Kirstein","sequence":"additional","affiliation":[{"name":"Department of Psychology, College of Arts and Sciences, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0144-2172","authenticated-orcid":false,"given":"Mark S.","family":"Kindy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA"},{"name":"Department of Psychology, College of Arts and Sciences, University of South Florida, Tampa, FL 33612, USA"},{"name":"Departments of Molecular Pharmacology and Physiology, Molecular Medicine, and Neurology, College of Medicine, University of South Florida, Tampa, FL 33612, USA"},{"name":"James A. Haley VA Medical Center, Tampa, FL 33612, USA"},{"name":"Shriners Hospital for Children, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/ejcn.2013.30","article-title":"Impact of nutritional status and dietary quality on stroke: Do we need specific recommendations?","volume":"67","author":"Lim","year":"2013","journal-title":"Eur. J. Clin. 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