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Yet, current clinical intervention strategies do not mitigate inflammation sequelae necessitating the development of innovative approaches to reduce inflammation and minimize deleterious effects of TBI. Herein, a subcutaneous formulation based on polymer of alpha\u2010ketoglutarate (paKG) delivering glycolytic inhibitor PFK15 (PFKFB3 inhibitor, a rate limiting step in glycolysis), alpha\u2010ketoglutarate (to fuel Krebs cycle) and peptide antigen from myelin proteolipid protein (PLP139\u2010151) is utilized as the prophylactic immunosuppressive formulation in a mouse model of TBI. In vitro, the paKG(PFK15+PLP) formulation stimulates proliferation of immunosuppressive regulatory T cells and induces generation of T helper\u20102 cells. When given subcutaneously in the periphery two weeks prior to mice sustaining a TBI, the formulation increases frequency of immunosuppressive macrophages and dendritic cells (DCs) in the periphery and the brain at day 7 post\u2010TBI and by 28 days post\u2010TBI enhanced PLP\u2010specific immunosuppressive cells infiltrate the brain. Immunohistology measurements of neuroinflammation are altered 28 days post\u2010TBI, spatial proteomics reveals evidence of enhanced autophagy in the injury penumbra, and the active formulation improves motor function. Overall, these data suggest that the TBI immunosuppressive formulation successfully induces an anti\u2010inflammatory profile and decreases TBI\u2010associated inflammation.<\/jats:p>","DOI":"10.1002\/adhm.202501417","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T03:27:36Z","timestamp":1748489256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Immunosuppressive Formulations for Immunological Defense against Traumatic Brain Injury"],"prefix":"10.1002","volume":"14","author":[{"given":"Kelly","family":"Lintecum","sequence":"first","affiliation":[{"name":"Biomedical Engineering School of Biological and Health Systems Engineering Arizona State University  Tempe AZ 85281 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhirami","family":"Thumsi","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Medicine Case Western Reserve 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