{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T12:05:15Z","timestamp":1779969915701,"version":"3.53.1"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":147,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001327"],"award-info":[{"award-number":["82001327"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To clarify the effects and mechanism of interleukin\u201017A (IL\u201017) in hyperglycemia (HG)\u2010induced blood\u2013brain barrier (BBB) breakdown following diffuse axonal injury (DAI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Differentially expressed proteins (DEPs) were identified by proteomic analysis via 4D\u2010SmartDIA between control and high\u2010glucose groups of BBB model established by bEnd.3 cells in vitro. A rat model of DAI was built using an instantaneous rotational damage device, and HG was mimicked by intraperitoneal (i.p.) injection of 50% glucose. The localization and expression of the IL\u201017 receptor (IL\u201017R) were tested by double\u2010label immunofluorescence and western blotting. IL\u201017 levels in brain tissue and serum, as well as the concentrations of inflammatory factors, were examined. Axonal injury morphology was evaluated via transmission electron microscopy (TEM) and immunohistochemical detection of \u03b2\u2010amyloid precursor protein (\u03b2\u2010APP) and neurofilament light chain and heavy chain (NF\u2010L, NF\u2010H). Glial response and apoptosis were also assessed. The detection of BBB permeability was via levels of Evans blue (EB) leakage and tight junction protein. The IL\u201017 pathway was inhibited using suberoylanilide hydroxamic acid (SAHA), and western blotting was used to detect the phosphorylation (p\u2010p65\/t\u2010p65 ratio) of the nuclear factor\u2010\u03baB (NF\u2010\u03baB) pathway. Oxidative stress levels were assessed via colorimetric assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Proteomic analysis revealed 444 upregulated and 159 downregulated proteins in high\u2010glucose\u2010stimulated bEnd.3 cells compared with those in normal cells, with the IL\u201017 signaling being one of the most significantly enriched pathways according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. IL\u201017 and IL\u201017R expression was elevated in brain tissue and serum following DAI, and HG further enhanced this upregulation; IL\u201017R was predominantly localized to vascular endothelial cells. HG aggravated axonal injury, increased cortical apoptosis and glial response, promoted BBB disruption, elevated proinflammatory factor levels, and increased oxidative stress after DAI. The inhibition of IL\u201017 reversed all the damage and protected BBB integrity by maintaining tight junctions and reducing the levels of proinflammatory factors and oxidative stress in vivo. Mechanistically, HG increased NF\u2010\u03baB p65 phosphorylation after DAI, whereas SAHA treatment significantly suppressed this phosphorylation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>IL\u201017 mediates HG\u2010induced axonal injury following DAI by destroying BBB integrity via NF\u2010\u03baB\u2010dependent inflammation and oxidative stress, signifying IL\u201017 as a target for mitigating neurovascular damage in hyperglycemic DAI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/mi\/6634285","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T11:39:01Z","timestamp":1779968341000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of IL\u201017 Alleviates Blood\u2013Brain Barrier Disruption Following Diffuse Axonal Injury Accompanied by Hyperglycemia Through the NF\u2010\u03baB 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