Hemorrhagic Shock Induces a Rapid Transcriptomic Shift of the Immune Balance in Leukocytes after Experimental Multiple Injury.

The immune response following trauma represents a major driving force of organ dysfunction and poor outcome. Therefore, we investigated the influence of an additional hemorrhagic shock (HS) on the early posttraumatic immune dysbalance in the whole population of blood leukocytes. A well-established murine polytrauma (PT) model with or without an additional pressure-controlled HS (mean arterial pressure of 30 mmHg (±5 mmHg) for 60 mins, afterwards fluid resuscitation with balanced electrolyte solution four times the volume of blood drawn) was used.

Role of the C5a-C5a receptor axis in the inflammatory responses of the lungs after experimental polytrauma and hemorrhagic shock.

Singular blockade of C5a in experimental models of sepsis is known to confer protection by rescuing lethality and decreasing pro-inflammatory responses. However, the role of inhibiting C5a has not been evaluated in the context of sterile systemic inflammatory responses, like polytrauma and hemorrhagic shock (PT + HS). In our presented study, a novel and highly specific C5a L-aptamer, NoxD21, was used to block C5a activity in an experimental murine model of PT + HS.

Remote Intestinal Injury Early After Experimental Polytrauma and Hemorrhagic Shock.

Dysfunction of the gut-blood barrier plays an important role in many diseases, such as inflammatory bowel disease, hemorrhagic shock (HS), or burn injury. However, little is known about gut barrier dysfunction after hemodynamically instable polytrauma (PT). Therefore, we aimed to evaluate the effects of PT and HS on remote intestinal damage and barrier dysfunction, especially regarding the role of zonula occludens protein 1 (ZO-1) as an important tight junction protein.

Inflammatory and apoptotic alterations in serum and injured tissue after experimental polytrauma in mice: distinct early response compared with single trauma or "double-hit" injury.

Background: The exact alterations of the immune system after polytrauma leading to sepsis and multiple-organ failure are poorly understood. Thus, the early local and systemic inflammatory and apoptotic response was characterized in a new polytrauma model and compared with the alterations seen after single or combined injuries.

Methods: Anesthetized C57BL/6 mice were subjected to either blunt bilateral chest trauma (Tx), closed head injury, right femur fracture including contralateral soft tissue injury, or a combination of injuries (PTx).

Silencing of fas, fas-associated via death domain, or caspase 3 differentially affects lung inflammation, apoptosis, and development of trauma-induced septic acute lung injury.

Activation of Fas signaling is a potentially important pathophysiological mechanism in the development of septic acute lung injury (ALI). However, so far the optimal targets within this signaling cascade remain elusive. Thus, we tested the hypothesis that in vivo gene silencing of Fas, Fas-associated via death domain (FADD), or caspase 3 by intratracheal administration of small interfering RNA would ameliorate ALI in a clinically relevant double-hit mouse model of trauma induced septic lung injury.