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Preclinical rodent trauma models are the mainstay of postinjury research but have been criticized for not fully replicating severe human trauma. The aim of this study was to create a rat model of multicompartmental injury which recreates profound traumatic injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male Sprague\u2013Dawley rats were subjected to unilateral lung contusion and hemorrhagic shock (LCHS), multicompartmental polytrauma (PT) (unilateral lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofracture), or na\u00efve controls. Weight, plasma toll\u2010like receptor 4 (TLR4), hemoglobin, spleen to body weight ratio, bone marrow (BM) erythroid progenitor (CFU\u2010GEMM, BFU\u2010E, and CFU\u2010E) growth, plasma granulocyte colony\u2010stimulating factor (G\u2010CSF) and right lung histologic injury were assessed on day 7, with significance defined as <jats:italic>p<\/jats:italic> values &lt;0.05 (*).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Polytrauma resulted in markedly more profound inhibition of weight gain compared to LCHS (<jats:italic>p<\/jats:italic>\u2009=\u20090.0002) along with elevated plasma TLR4 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), lower hemoglobin (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), and enlarged spleen to body weight ratios (<jats:italic>p<\/jats:italic>\u2009=\u20090.004). Both LCHS and PT demonstrated suppression of CFU\u2010E and BFU\u2010E growth compared to na\u00efve (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.03, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Plasma G\u2010CSF was elevated in PT compared to both na\u00efve and LCHS (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001, <jats:italic>p<\/jats:italic>\u2009=\u20090.02). LCHS and PT demonstrated significant histologic right lung injury with poor alveolar wall integrity and interstitial edema.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Multicompartmental injury as described here establishes a reproducible model of multicompartmental injury with worsened anemia, splenic tissue enlargement, weight loss, and increased inflammatory activity compared to a less severe model. This may serve as a more effective model to recreate profound traumatic injury to replicate the human inflammatory response postinjury.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12447","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T16:50:51Z","timestamp":1718124651000},"page":"367-376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A rat model of multicompartmental traumatic injury and hemorrhagic shock induces bone marrow dysfunction and profound anemia"],"prefix":"10.1002","volume":"7","author":[{"given":"Lauren S.","family":"Kelly","sequence":"first","affiliation":[{"name":"Department of Surgery and Sepsis and Critical Illness Research Center University of Florida College of Medicine  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2729-7126","authenticated-orcid":false,"given":"Jennifer A.","family":"Munley","sequence":"additional","affiliation":[{"name":"Department of Surgery and Sepsis and Critical Illness Research Center University of Florida College of Medicine  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2538-3576","authenticated-orcid":false,"given":"Erick E.","family":"Pons","sequence":"additional","affiliation":[{"name":"Department of Surgery and Sepsis and Critical Illness Research Center University of Florida College of Medicine  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kolenkode B.","family":"Kannan","sequence":"additional","affiliation":[{"name":"Department of Surgery and Sepsis and Critical Illness Research Center University of Florida College of Medicine  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth 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