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Therefore, the objective of this study was to determine the efficacy of methylene blue (MB), an antioxidant agent, in reducing inflammation and behavioral complications associated with a diffuse brain injury. Here we show that immediate MB infusion (intravenous; 15\u201330 minutes after TBI) reduced cerebral edema, attenuated microglial activation and reduced neuroinflammation, and improved behavioral recovery after midline fluid percussion injury in mice. Specifically, TBI-associated edema and inflammatory gene expression in the hippocampus were significantly reduced by MB at 1\u2009d post injury. Moreover, MB intervention attenuated TBI-induced inflammatory gene expression (interleukin [IL]-1\u03b2, tumor necrosis factor \u03b1) in enriched microglia\/macrophages 1\u2009d post injury. Cell culture experiments with lipopolysaccharide-activated BV2 microglia confirmed that MB treatment directly reduced IL-1\u03b2 and increased IL-10 messenger ribonucleic acid in microglia. Last, functional recovery and depressive-like behavior were assessed up to one week after TBI. MB intervention did not prevent TBI-induced reductions in body weight or motor coordination 1\u20137\u2009d post injury. Nonetheless, MB attenuated the development of acute depressive-like behavior at 7\u2009d post injury. Taken together, immediate intervention with MB was effective in reducing neuroinflammation and improving behavioral recovery after diffuse brain injury. Thus, MB intervention may reduce life-threatening complications of TBI, including edema and neuroinflammation, and protect against the development of neuropsychiatric complications.<\/jats:p>","DOI":"10.1089\/neu.2014.3514","type":"journal-article","created":{"date-parts":[[2014,7,29]],"date-time":"2014-07-29T07:01:28Z","timestamp":1406617288000},"page":"127-138","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":89,"title":["Methylene Blue Attenuates Traumatic Brain Injury-Associated Neuroinflammation and Acute Depressive-Like Behavior in Mice"],"prefix":"10.1177","volume":"32","author":[{"given":"Ashley M.","family":"Fenn","sequence":"first","affiliation":[{"name":"Ohio State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Skendelas","sequence":"additional","affiliation":[{"name":"Ohio State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel N.","family":"Moussa","sequence":"additional","affiliation":[{"name":"Ohio State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan M.","family":"Muccigrosso","sequence":"additional","affiliation":[{"name":"Ohio State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip G.","family":"Popovich","sequence":"additional","affiliation":[{"name":"Ohio State University"},{"name":"Ohio State University"},{"name":"Ohio State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Lifshitz","sequence":"additional","affiliation":[{"name":"University of Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S.","family":"Eiferman","sequence":"additional","affiliation":[{"name":"Ohio State University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Godbout","sequence":"additional","affiliation":[{"name":"Ohio State University"},{"name":"Ohio State University"},{"name":"Ohio State University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2015,1,15]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"National Hospital Discharge Survey (NHDS) 2010. 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