{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:57:52Z","timestamp":1790618272594,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess whether pioglitazone (Pio) protects against sepsis\u2010associated encephalopathy (SAE) and to probe underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sepsis was induced in male C57BL\/6 mice by caecal ligation and puncture (CLP). At 24\u2009h post\u2010CLP, mice received Pio and\/or the PPAR\u2010\u03b3 antagonist GW9662 and were followed for 14\u2010day survival. Cognitive and affective behaviors were evaluated using a behavioral battery. Blood\u2013brain barrier (BBB) permeability was assessed by Evans blue extravasation, and hippocampal inflammatory and apoptotic readouts were examined by ELISA, immunoblotting, and TUNEL staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CLP reduced 14\u2010day survival to 21.82%, whereas Pio increased survival to 46.15%; GW9662 abolished this benefit (19.36%). Pio improved behavior consistent with reduced anxiety\u2010like behavior and better learning\/memory. Mechanistically, Pio decreased Evans blue leakage and increased Claudin\u20105, suppressed TLR4\/NF\u2010\u03baB\u2013associated inflammation (lower TNF\u2010\u03b1, IL\u20101\u03b2, and IL\u20106; higher IL\u201010), and reduced neuronal apoptosis; these effects were largely reversed by GW9662.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pioglitazone alleviates sepsis\u2010induced brain dysfunction and improves survival in mice in a PPAR\u2010\u03b3\u2013dependent manner.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71103","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:24:40Z","timestamp":1788150280000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>PPAR\u03b3<\/scp>\n                    \u2010Dependent Pioglitazone Treatment Suppresses Neuroinflammation and Improves Cognition in Sepsis\u2010Associated Encephalopathy in Mice"],"prefix":"10.1002","volume":"32","author":[{"given":"Jing","family":"Zhang","sequence":"first","affiliation":[{"name":"Intensive Care Unit Yuebei People's Hospital of Shantou University Medical  Shaoguan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9137-7211","authenticated-orcid":false,"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Neurosurgery The Second Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9012-3898","authenticated-orcid":false,"given":"Nan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine General Hospital of Northern Theater Command  Shenyang Liaoning 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