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In our previous study, we found that <jats:italic>Fat1<\/jats:italic>\n            <jats:sup>+<\/jats:sup>-transgenic mice with higher endogenous n-3 polyunsaturated fatty acids (n-3 PUFA) were protected from post-TBI behavioral deficits and exhibited reduced levels of TBI-induced microglial activation, inflammatory factors, and sphingolipid ceramide, a lipid mediator of inflammation and cell death. This study\u2019s objective was to evaluate if feeding n-3 PUFA (EPA and docosahexaenoic acid, DHA 2:1) could restrict the elevation of ceramide in brain tissue and prevent TBI-mediated sensory-motor and behavioral deficits. Wildtype C57\/BL6 mice were gavage pre-fed with PUFA (EPA: DHA\u2009=\u20092:1) at 500\u00a0mg\/kg body weight\/week for 2\u00a0weeks before and 4\u00a0weeks after exposure to left side focal cranial air-blast (50 psi) TBI or sham-blast (0-psi). Saline-gavaged mice served as controls. Following blast injury, various motor, visual, and behavioral tests were conducted, and brain tissues were collected for histological and biochemical assays. Lipidomics analysis confirmed a significant elevation of EPA in the plasma and brain tissue of PUFA-fed mice. TBI-Blast brain tissues were found to have elevated ceramide levels in control mice but not in PUFA-fed mice. Moreover, PUFA-fed mice demonstrated protection against motor impairment, photoreceptor dysfunction, depression, oculomotor nerve degeneration, and microglia activation in the optic tract. Our results demonstrate that EPA-mediated suppression of ceramide biosynthesis and neuroinflammatory factors in PUFA-fed mice is associated with significant protection against the visual, motor, and emotional deficits caused by TBI.<\/jats:p>","DOI":"10.1007\/s12035-025-05019-9","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T13:37:00Z","timestamp":1746797820000},"page":"11972-11985","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Oral Supplementation of n-3 Polyunsaturated Fatty Acids (n-3-PUFA) Can Prevent TBI-Induced Visual, Motor, and Emotional Deficits in Mice"],"prefix":"10.1007","volume":"62","author":[{"given":"Koushik","family":"Mondal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashlyn A.","family":"Gary","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anisha","family":"Dash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobel A.","family":"Del Mar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Stephenson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles E.","family":"Chalfant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Reiner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"Sears","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nawajes","family":"Mandal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"issue":"2","key":"5019_CR1","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1111\/j.1468-1331.2011.03581.x","volume":"19","author":"PE Vos","year":"2012","unstructured":"Vos PE, Alekseenko Y, Battistin L, Ehler E, Gerstenbrand F, Muresanu DF et al (2012) Mild traumatic brain injury. 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