{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:29:32Z","timestamp":1789046972835,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>The present work investigated the expression and function of Lgals3 in cerebral ischemia\/reperfusion (cerebral IR) injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Differentially expressed genes in cerebral IR were analyzed by the Gene Expression Omnibus (GEO) microarray. A middle cerebral artery occlusion (MCAO) mouse model was constructed. Adeno\u2010associated virus serotype 9 vector carrying Lgals3 shRNA was administered to mice via tail vein injection. Four weeks after virus administration, mice were subjected to MCAO modeling. Neurological function was reflected by evaluating the neurological deficit score. To assess infarct size and neuronal apoptosis, triphenyl tetrazolium chloride (TTC) staining and TUNEL assay were performed. The concentrations of IL\u20106, TNF\u2010\u03b1, IL\u20104, and IL\u20101\u03b2 in brain tissues were measured using enzyme\u2010linked immunosorbent assay (ELISA). Co\u2010immunoprecipitation (Co\u2010IP) was performed to examine the interaction between Lgals3 and TLR4. In addition, real\u2010time quantitative reverse transcription\u2010polymerase chain reaction (qRT\u2010PCR) and Western blotting were employed to analyze gene and protein expression levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GEO bioinformatics analysis revealed that Lgals3 expression was significantly upregulated in cerebral IR. MCAO mouse model was successfully established, and Lgals3 was markedly upregulated in brain tissues of MCAO mice. Lgals3 knockdown reduced infarct volume, improved neurological deficit scores, and inhibited neuronal apoptosis, accompanied by decreased levels of pro\u2010inflammatory cytokines (IL\u20106, TNF\u2010\u03b1, and IL\u20101\u03b2) and increased levels of anti\u2010inflammatory cytokine IL\u20104 in brain tissues of MCAO mice. Lgals3 silencing inhibited the activation of the TLR4\/MyD88\/NF\u2010\u03baB pathway, as evidenced by downregulated expression of TLR4, MyD88, p\u2010p65, and p65. Co\u2010IP experiment confirmed a direct interaction between Lgals3 and TLR4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Lgals3 knockdown alleviates neuroinflammation and neuronal apoptosis in brain tissues of mice with cerebral IR injury. The present findings indicate that Lgals3 participates in the progression of cerebral IR injury, and may serve as a potential intervention target for ameliorating cerebral IR damage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71700","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T06:38:39Z","timestamp":1787294319000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Downregulation of Lgals3 Alleviates Inflammatory Response and Apoptosis in a Mouse Model of Cerebral Ischemia\/Reperfusion Injury"],"prefix":"10.1002","volume":"16","author":[{"given":"Zhaodan","family":"Gan","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine The First Affiliated Hospital of Nanjing Medical University  Nanjing 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