Modeling acute traumatic injury

Acute traumatic injury is a complex disease that has remained a leading cause of death, which affects all ages in our society. Direct mechanical insult to tissues may result in physiological and immunologic disturbances brought about by blood loss, coagulopathy, as well as ischemia and reperfusion insults. This inappropriate response leads to an abnormal release of endogenous mediators of inflammation that synergistically contribute to the incidence of morbidity and mortality. This aberrant activation and suppression of the immune system follows a bimodal pattern, wherein activation of the innate immune responses is followed by an anti-inflammatory response with suppression of the adaptive immunity, which can subsequently lead secondary insults and multiple organ dysfunction. Traumatic injury rodent and swine models have been used to describe many of the underlying pathologic mechanisms, which have led to an improved understanding of the morbidity and mortality associated with critically ill trauma patients. The enigmatic immunopathology of the human immunologic response after severe trauma, however, has never more been apparent and there grows a need for a clinically relevant animal model, which mimics this immune physiology to enhance the care of the most severely injured. This has necessitated preclinical studies in a more closely related model system, the nonhuman primate. In this review article, we summarize animal models of trauma that have provided insight into the clinical response and understanding of cellular mechanisms involved in the onset and progression of ischemia–reperfusion injury as well as describe future treatment options using immunomodulation-based strategies.