{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T03:24:07Z","timestamp":1788146647880,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874262"],"award-info":[{"award-number":["81874262"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173519"],"award-info":[{"award-number":["82173519"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To demonstrate the role of IL\u20106 and pSTAT3 in the inflammatory response to cerebral ischemia\/reperfusion following folic acid deficiency (FD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The middle cerebral artery occlusion\/reperfusion (MCAO\/R) model was established in adult male Sprague\u2010Dawley rats in vivo, and cultured primary astrocytes were exposed to oxygen\u2010glucose deprivation\/reoxygenation (OGD\/R) to emulate ischemia\/reperfusion injury in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Glial fibrillary acidic protein (GFAP) expression significantly increased in astrocytes of the brain cortex in the MCAO group compared to the SHAM group. Nevertheless, FD did not further promote GFAP expression in astrocytes of rat brain tissue after MCAO. This result was further confirmed in the OGD\/R cellular model. In addition, FD did not promote the expressions of TNF\u2010\u03b1 and IL\u20101\u03b2 but raised IL\u20106 (Peak at 12\u2009h after MCAO) and pSTAT3 (Peak at 24\u2009h after MCAO) levels in the affected cortices of MCAO rats. In the in vitro model, the levels of IL\u20106 and pSTAT3 in astrocytes were significantly reduced by treatment with Filgotinib (JAK\u20101 inhibitor) but not AG490 (JAK\u20102 inhibitor). Moreover, the suppression of IL\u20106 expression reduced FD\u2010induced increases in pSTAT3 and pJAK\u20101. In turn, inhibited pSTAT3 expression also depressed the FD\u2010mediated increase in IL\u20106 expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>FD led to the overproduction of IL\u20106 and subsequently increased pSTAT3 levels via JAK\u20101 but not JAK\u20102, which further promoted increased IL\u20106 expression, thereby exacerbating the inflammatory response of primary astrocytes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14116","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T09:21:30Z","timestamp":1676539290000},"page":"1537-1546","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Folic acid deficiency exacerbates the inflammatory response of astrocytes after ischemia\u2010reperfusion by enhancing the interaction between <scp>IL<\/scp>\u20106 and <scp>JAK<\/scp>\u20101\/<scp>pSTAT3<\/scp>"],"prefix":"10.1111","volume":"29","author":[{"given":"Man","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Environment, Nutrition and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Environment, Nutrition and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health Tianjin Medical University  Tianjin 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