Neutrophil Gelatinase-Associated Lipocalin: A Shared Early Biomarker of Remote Organ Dysfunction in Blast-Induced Extremity Trauma

Polytrauma is a critical global health concern characterized by immune dysregulation and a high risk of multiple organ dysfunction syndrome (MODS). Early molecular mechanisms linking trauma severity to organ injury are poorly understood. We used two rat blast-polytrauma models: a tourniquet-induced ischemia/reperfusion injury (tIRI) model and a non-ischemia/reperfusion injury (non-IRI) model. Naïve animals served as controls. RT-qPCR of 120 inflammatory genes in the lung, kidney, and liver, combined with STRING protein-protein interaction analysis, revealed distinct yet overlapping inflammatory gene signatures across all the organs. A core set of genes (<i>Il6</i>, <i>Lbp</i>, <i>Nos2</i>, and <i>Lcn2</i>) was consistently upregulated, indicating shared inflammatory pathways. Transcriptomic responses were most pronounced in the tIRI group, with greater magnitude and altered temporal dynamics, uniquely amplifying pro-inflammatory cytokines, immune cell activators, chemokines, and tissue damage markers. Lipocalin-2 (<i>Lcn2</i>/NGAL) emerged as a shared hub gene across all the organs within 24 h post-injury. Its expression significantly correlated with MODS activity and adverse outcomes, independent of the injury model. At 168 h, <i>Lcn2</i> expression correlated with increased liver damage and NGAL levels correlated with tissue trauma severity. These findings elucidate distinct pro-inflammatory mediators and networks underlying secondary organ dysfunction, highlighting NGAL as a potential universal biomarker of trauma-induced inflammation and MODS activity, suggesting it as a therapeutic target.