{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:23:35Z","timestamp":1792686215393,"version":"4.5.0"},"reference-count":70,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 105-2314-B-075A-004-MY3 and MOST 105-2314-B-075A-006-MY3"],"award-info":[{"award-number":["MOST 105-2314-B-075A-004-MY3 and MOST 105-2314-B-075A-006-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Taichung Veterans General Hospital, Taiwan","award":["TCVGH-1108201C and TCVGH-HK1098001"],"award-info":[{"award-number":["TCVGH-1108201C and TCVGH-HK1098001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Poststroke hyperglycemia and inflammation have been implicated in the pathogenesis of stroke. Janus Kinase 2 (Jak2), a catalytic signaling component for cytokine receptors such as Interleukin-6 (IL-6), has inflammatory and metabolic properties. This study aimed to investigate the roles of Jak2 in poststroke inflammation and metabolic abnormality in a rat model of permanent cerebral ischemia. Pretreatment with Jak2 inhibitor AG490 ameliorated neurological deficit, brain infarction, edema, oxidative stress, inflammation, caspase-3 activation, and Zonula Occludens-1 (ZO-1) reduction. Moreover, in injured cortical tissues, Tumor Necrosis Factor-\u03b1, IL-1\u03b2, and IL-6 levels were reduced with concurrent decreased NF-\u03baB p65 phosphorylation, Signal Transducers and Activators of Transcription 3 phosphorylation, Ubiquitin Protein Ligase E3 Component N-Recognin 1 expression, and Matrix Metalloproteinase activity. In the in vitro study on bEnd.3 endothelial cells, AG490 diminished IL-6-induced endothelial barrier disruption by decreasing ZO-1 decline. Metabolically, administration of AG490 lowered fasting glucose, with improvements in glucose intolerance, plasma-free fatty acids, and plasma C Reactive Proteins. In conclusion, AG490 improved the inflammation and oxidative stress of neuronal, hepatic, and muscle tissues of stroke rats as well as impairing insulin signaling in the liver and skeletal muscles. Therefore, Jak2 blockades may have benefits for combating poststroke central and peripheral inflammation, and metabolic abnormalities.<\/jats:p>","DOI":"10.3390\/antiox10121958","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T09:52:29Z","timestamp":1638870749000},"page":"1958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Jak2 Inhibitor AG490 Improved Poststroke Central and Peripheral Inflammation and Metabolic Abnormalities in a Rat Model of Ischemic Stroke"],"prefix":"10.3390","volume":"10","author":[{"given":"Ya-Yu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Family Medicine, Taichung Veterans General Hospital, Taichung City 407, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1901-2656","authenticated-orcid":false,"given":"Shih-Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei City 112, Taiwan"},{"name":"Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, Taichung City 407, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Yi","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Feng Yuan Hospital, Taichung City 420, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Cheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Taichung Veterans General Hospital, Taichung City 407, Taiwan"},{"name":"Department of Financial Engineering, Providence University, Taichung City 433, Taiwan"},{"name":"Department of Data Science and Big Data Analytics, Providence University, Taichung City 433, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5105-5285","authenticated-orcid":false,"given":"Wen-Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, National Chung Hsing University, Taichung City 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Lan","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung City 407, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Fan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science, I-Shou University, Kaohsiung City 840, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nursing, Hung Kuang University, Taichung City 433, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Jung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung City 407, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung City 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jstrokecerebrovasdis.2018.09.013","article-title":"Epidemiology and outcomes of ischemic stroke and transient ischemic attack in the adult and geriatric population","volume":"28","author":"Navis","year":"2019","journal-title":"J. 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