{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T01:12:20Z","timestamp":1777770740016,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"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":["Brain and Behavior"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ischemic stroke (IS) is a common neurological disease with a significant financial burden but lacks effective drugs. This study sought to explore the mechanisms underlying MAP kinase\u2010interacting serine\/threonine\u2010protein kinase 2 (MKNK2), a gene enriched in the hypoxia\u2010inducible factor\u20101 (HIF\u20101) signaling, in IS\u2010related neurological injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Middle cerebral artery occlusion\/reperfusion (MCAO\/R) and oxygen\u2010glucose deprivation\/reoxygenation (OGD\/R) models were used in vivo and in vitro. Rats were infected with lentiviral vectors harboring knockdown or overexpression of the target genes, followed by MCAO\/R to conduct 2,3,5\u2010triphenyltetrazolium chloride, HE, Fluoro\u2010Jade C, and TUNEL, enzyme\u2010linked immunosorbent assay, immunohistochemistry, and neurological deficits assessment. The regulation of Krueppel\u2010like factor 7 (KLF7) on MKNK2 was analyzed by ChIP and dual\u2010luciferase assays. The effects of the KLF7\/MKNK2\/HIF\u20101 axis on the M1 or M2 polarization of rat microglia were demonstrated by the transfection of knockdown or overexpression plasmids into the cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MCAO\/R\u2010treated rat brain tissues and OGD\/R\u2010treated rat microglia showed MKNK2 upregulation along with activation of the HIF\u20101 signaling, whereas KLF7 expression was downregulated. Knockdown of MKNK2 inhibited the HIF\u20101 signaling and M1 microglia polarization, whereas it promoted M2 polarization. KLF7 repressed the MKNK2 transcription, thereby achieving the same effect as the knockdown of MKNK2 in vitro, which was reversed by combined overexpression of MKNK2. Knockdown of MKNK2 or overexpression of KLF7 ameliorated MCAO\/R\u2010induced brain damage and neurological injury in rats. MKNK2 overexpression reversed the alleviating effect of KLF7 overexpression on pathological brain injury in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Significant downregulation of KLF7 expression after IS exacerbated pathological brain damage through the MKNK2\u2010mediated HIF\u20101 pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70850","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T08:37:56Z","timestamp":1757407076000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["KLF7 Blocks MKNK2\/HIF\u20101 Pathway\u2010Mediated M1 Microglia Polarization to Ameliorate Ischemic Stroke\u2010Induced Neurological Injury"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5206-5575","authenticated-orcid":false,"given":"Ran","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang P. 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