{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:10:53Z","timestamp":1788268253621,"version":"build-2803163510"},"reference-count":67,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["EEQ\/2022\/000997"],"award-info":[{"award-number":["EEQ\/2022\/000997"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Sepsis is a life threatening condition which triggers multiple organ failure. Sepsis\u2010associated encephalopathy (SAE) is more prevalent form of sepsis which involves acute and long\u2010term cerebral impairment. JAK\/STAT pathway is one of the most crucial signaling cascades which promote neuroinflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The present investigation was designed to explore the possible role of JAK\/STAT inhibitors in sepsis\u2010induced cerebral injury and cognitive impairment in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Swiss Albino mice underwent cecal ligation and puncture (CLP) to induce sepsis\u2010associated cognitive deficits. Tofacitinib and baricitinib were administered orally one hour before CLP, followed by six days post\u2010CLP administration. From days 7\u201012, behavioral changes were assessed through various tests, including open field (locomotor activity and non\u2010associative memory), inhibitory avoidance (aversive memory), novel object recognition (recognition memory), and Morris\u2010Water maze tests (spatial learning and memory). Neuronal injury (S\u2010100 calcium\u2010binding protein B, S100B and neuronal specific enolase, NSE) and inflammation (TNF\u2010\u03b1) were assessed in the serum. Further, oxidative changes in the mouse brain were evaluated by measuring malondialdehyde and reduced glutathione levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>JAK\/STAT inhibitors, including tofacitinib (7.5 and 15 mg\/kgper os) and baricitinib (5 and 10 mg\/kgper os), significantly ameliorated sepsis\u2010induced deficits in non\u2010associative, aversive, recognition and spatial memory in mice. Further, tofacitinib and baricitinib treatment decreased TNF\u2010\u03b1, Malondialdehyde, S\u2010100B and NSE in mice with sepsis while increasing the levels of reduced glutathione.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>JAK\/STAT inhibitors significantly decreased neuroinflammation, oxidative stress, and neuronal damage while enhancing cognitive function.<\/jats:p><\/jats:sec>","DOI":"10.1111\/fcp.70005","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T11:36:34Z","timestamp":1744025794000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["JAK\/STAT inhibitors mitigate sepsis\u2010associated cerebral and cognitive injury"],"prefix":"10.1111","volume":"39","author":[{"given":"Mohini Singh","family":"Bhadauriya","sequence":"first","affiliation":[{"name":"Department of Pharmacology Central University of Punjab  Ghudda, Bathinda 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