Temporal Evolution and Dissociation of Neuroendocrine Stress Inflammatory Responses Neurological Dysfunction and Multiorgan Injury Following Experimental Polytrauma in Mice

Polytrauma induces neuroendocrine, inflammatory, neurological, and multiorgan responses that may follow distinct temporal trajectories. We characterized these changes during the first 7 days after experimental head–thorax–abdomen polytrauma in male C57BL/6 mice. Animals underwent polytrauma or Sham procedures and were evaluated at 0 h, 3 h, 6 h, 12 h, 24 h, 3 d and 7 d. Neurological and behavioral outcomes, brain water content, serum and injured-brain neuroendocrine and inflammatory mediators, and brain, lung, and liver histopathology were assessed. Polytrauma caused persistent neurological and locomotor impairment and increased brain water content. Corticosterone rose rapidly during the early phase and largely normalized by 12 h, whereas norepinephrine in injured brain tissue increased at 3–7 d. Pro- and anti-inflammatory mediators showed distinct systemic and cerebral temporal profiles. Histology demonstrated time-dependent brain, lung, and liver injury with evolving extracellular matrix remodeling. Thus, experimental polytrauma produces temporally dissociated responses characterized by early glucocorticoid activation, persistent neurological and inflammatory abnormalities, delayed cerebral noradrenergic changes, and progressive multiorgan remodeling, supporting phase-specific pathophysiology after injury.