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The present study evaluated the therapeutic effects of intravenous immunoglobin (IVIg), a well-established immunomodulatory treatment, in a controlled cortical impact model of severe TBI in mice. The beneficial effects of IVIg treatment on acute neurological status, motor function, anxiety level, and spatial learning ability were demonstrated by reduced Neurological Severity Scores, increased Rotarod latency and cumulative movement durations in open-field tests, and improved active place avoidance performance. IVIg treatment also significantly reduced brain tissue loss, which was examined using Nissl staining at 16 weeks after TBI. Furthermore, brain microRNAs (miRNAs) were profiled to identify the biological pathways potentially associated with the actions of IVIg treatment using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. To identify potential peripheral biomarkers reflecting the changes in the brain, differentially expressed miRNAs in plasma and brain samples from the same animals were compared. Our immunostaining results showed that IVIg treatment significantly attenuated the upregulation of IL-1\u03b2 and complement 3 (C3) and altered the activation of microglia and astrocytes. This proof-of-concept study provided strong evidence for the beneficial effects of IVIg treatment in severe penetrating TBI.<\/jats:p>","DOI":"10.1177\/08977151251401566","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T16:17:12Z","timestamp":1767111432000},"page":"996-1013","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Beneficial Effects of Intravenous Immunoglobulin Treatment in a Mouse Preclinical Model of Severe Traumatic Brain Injury"],"prefix":"10.1177","volume":"43","author":[{"given":"Min","family":"Chen","sequence":"first","affiliation":[{"name":"Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noora","family":"Puhakka","sequence":"additional","affiliation":[{"name":"A.I. 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