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Within minutes after SCI, activated microglia and astrocytes produce proinflammatory mediators such as TNF\u2010\u03b1, IL\u20106, iNOS, and COX\u20102 which induce tissue injury through cytotoxicity, vascular hyperpermeability, and secondary ischemia. The inflammatory cascade is amplified by chemokines like CCL2 and CXCL1 which recruit immune cells to the injured site. HuR is an RNA regulator that promotes glial expression of many proinflammatory factors by binding to adenylate\u2010 and uridylate\u2010rich elements in the 3' untranslated regions of their mRNAs. SRI\u201042127 is a small molecule which blocks HuR function by preventing its nucleocytoplasmic translocation. This study aimed to evaluate the potential of SRI\u201042127 to suppress neuroinflammation after SCI and improve functional outcome. Adult female mice underwent a T10 contusion injury and received SRI\u201042127 1\u2009h post injury for up to 5\u2009days. Locomotor function was assessed by open field testing, balance beam, and rotarod. Immunohistochemistry was used to assess lesion size, neuronal loss, myelin sparing, microglial\/astroglial activation, and HuR localization. Inflammatory mediator expression was assessed by qPCR, immunohistochemistry, ELISA, or western blot. We found that SRI\u201042127 treatment significantly attenuated loss of locomotor function and post\u2010SCI pain. There was a reduction in lesion size and neuronal loss with an increase in myelin sparing. Microglia and astrocytes showed reduced activation and reduced nucleocytoplasmic translocation of HuR. There was a striking suppression of proinflammatory mediators at the epicenter along with peripheral suppression of inflammatory responses in serum, liver, and spleen. In conclusion, HuR inhibition with SRI\u201042127 may be a viable therapeutic approach for suppressing neuroinflammatory responses after SCI and improving functional outcome.<\/jats:p>","DOI":"10.1096\/fj.202500236r","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T08:49:37Z","timestamp":1746175777000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Inhibition of the\n                    <scp>RNA<\/scp>\n                    Regulator\n                    <scp>HuR<\/scp>\n                    Mitigates Spinal Cord Injury by Potently Suppressing Post\u2010Injury Neuroinflammation"],"prefix":"10.1096","volume":"39","author":[{"given":"Mohammed Amir","family":"Husain","sequence":"first","affiliation":[{"name":"Department of Neurology University of Alabama at Birmingham  Birmingham Alabama USA"},{"name":"Killion Center for Neurodegeneration and Experimental Therapeutics University of Alabama at Birmingham  Birmingham Alabama USA"},{"name":"Birmingham Veterans Affairs Health Care System  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reed","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Alabama at Birmingham  Birmingham Alabama USA"},{"name":"Killion Center for Neurodegeneration and Experimental Therapeutics University of Alabama at Birmingham  Birmingham Alabama USA"},{"name":"Birmingham Veterans Affairs Health Care System  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Sorge","sequence":"additional","affiliation":[{"name":"Birmingham Veterans Affairs Health Care System  Birmingham Alabama USA"},{"name":"Department of Psychology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulraheem","family":"Kaimari","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Si","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Alabama at Birmingham  Birmingham Alabama USA"},{"name":"Killion Center for Neurodegeneration and Experimental Therapeutics University of Alabama at Birmingham  Birmingham Alabama USA"},{"name":"Birmingham Veterans Affairs Health Care System  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Z.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Guha","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Alabama at Birmingham  Birmingham Alabama USA"},{"name":"Killion Center for Neurodegeneration and Experimental Therapeutics University of Alabama at Birmingham  Birmingham Alabama USA"},{"name":"Birmingham Veterans Affairs Health Care System  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Alabama at Birmingham  Birmingham Alabama USA"},{"name":"Killion Center for Neurodegeneration and Experimental Therapeutics University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P.","family":"Cardozo","sequence":"additional","affiliation":[{"name":"Spinal Cord Damage Research Center, James J. 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