A Rat Model of Multicompartmental Traumatic Injury and Hemorrhagic Shock Induces Bone Marrow Dysfunction and Profound Anemia

Overview

Journal Animal Model Exp Med

Date 2024 Jun 11

PMID 38860566

Authors

Lauren S Kelly

Jennifer A Munley

Erick E Pons

Kolenkode B Kannan

Elizabeth M Whitley

Letitia E Bible

Philip A Efron

Alicia M Mohr

Affiliations

Soon will be listed here.

Abstract

Background: Severe trauma is associated with systemic inflammation and organ dysfunction. 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.

Methods: Male Sprague-Dawley rats were subjected to unilateral lung contusion and hemorrhagic shock (LCHS), multicompartmental polytrauma (PT) (unilateral lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofracture), or naïve controls. Weight, plasma toll-like receptor 4 (TLR4), hemoglobin, spleen to body weight ratio, bone marrow (BM) erythroid progenitor (CFU-GEMM, BFU-E, and CFU-E) growth, plasma granulocyte colony-stimulating factor (G-CSF) and right lung histologic injury were assessed on day 7, with significance defined as p values <0.05 (*).

Results: Polytrauma resulted in markedly more profound inhibition of weight gain compared to LCHS (p = 0.0002) along with elevated plasma TLR4 (p < 0.0001), lower hemoglobin (p < 0.0001), and enlarged spleen to body weight ratios (p = 0.004). Both LCHS and PT demonstrated suppression of CFU-E and BFU-E growth compared to naïve (p < 0.03, p < 0.01). Plasma G-CSF was elevated in PT compared to both naïve and LCHS (p < 0.0001, p = 0.02). LCHS and PT demonstrated significant histologic right lung injury with poor alveolar wall integrity and interstitial edema.

Conclusions: 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.

Citing Articles

A rat model of multicompartmental traumatic injury and hemorrhagic shock induces bone marrow dysfunction and profound anemia.

Kelly L, Munley J, Pons E, Kannan K, Whitley E, Bible L Animal Model Exp Med. 2024; 7(3):367-376.

PMID: 38860566 PMC: 11228100. DOI: 10.1002/ame2.12447.

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