Peroxiredoxin VI oxidation in cerebrospinal fluid correlates with traumatic brain injury outcome

Traumatic brain injury (TBI) patients would benefit from the identification of reliable biomarkers to predict outcomes and treatment strategies. In our study, cerebrospinal fluid (CSF) from patients with severe TBI was evaluated for oxidant stress-mediated damage progression after hospital admission and subsequent ventriculostomy placement. Interestingly, substantial levels of peroxiredoxin VI (Prdx6), a major antioxidant enzyme normally found in astrocytes, were detected in CSF from control and TBI patients and were not associated with blood contamination. Functionally, Prdx6 and its associated binding partner glutathione S-transferase Pi (GSTP1-1, also detected in CSF) act in tandem to detoxify lipid peroxidation damage to membranes. We found Prdx6 was fully active in CSF of control patients but becomes significantly inactivated (oxidized) in TBI. Furthermore, significant and progressive oxidation of “buried” protein thiols in CSF of TBI patients (compared to those of nontrauma controls) was detected over a 24-h period after hospital admission, with increased oxidation correlating with severity of trauma. Conversely, recovery of Prdx6 activity after 24 h indicated more favorable patient outcome. Not only is this the first report of an extracellular form of Prdx6 but also the first report of its detection at a substantial level in CSF. Taken together, our data suggest a meaningful correlation between TBI-initiated oxidation of Prdx6, its specific phospholipid hydroperoxide peroxidase activity, and severity of trauma outcome. Consequently, we propose that Prdx6 redox status detection has the potential to be a biomarker for TBI outcome and a future indicator of therapeutic efficacy.     

A model of hemorrhagic shock and acute lung injury in Landrace-Large White Swine

Traumatic injury is a leading cause of death worldwide for people between 5 and 44 y of age, and it accounts for 10% of all deaths. The incidence of acute lung injury, a life-threatening complication in severely injured trauma patients remains between 30% and 50%. This study describes an experimental protocol of volume-controlled hemorrhage in Landrace-Large White swine. The experimental approach simulated the clinical situation associated with hemorrhagic shock in the trauma patient while providing controlled conditions to maximize reproducibility. The duration of the protocol was 8 h and was divided into 5 distinct phases-stabilization, hemorrhage, maintenance, resuscitation, and observation-after which the swine were euthanized. Lung tissue samples were analyzed histologically. All swine survived the protocol. The hemodynamic responses accurately reflected those seen in humans, and the development of acute lung injury was consistent among all swine. This experimental protocol of hemorrhagic shock and fluid resuscitation in Landrace-Large White swine may be useful for future study of hemorrhagic shock and acute lung injury.     

Pediatric trauma: differences in pathophysiology,injury patterns and treatment compared with adult trauma.

Although multiple trauma remains the leading cause of death among children, fewer resources and less attention have been directed to treatment of the injured child than to treatment of the injured adult. Insufficient training of medical personnel and hence lack of expertise in the management of injured children are factors contributing to disability and death in such children. Although the principles of resuscitation of injured children are similar to those for adults, appreciation of the differences in cardiorespiratory variables, airway anatomy, response to blood loss, thermoregulation and equipment required is essential for successful initial resuscitation. Cerebral, abdominal and thoracic injuries account for most of the disability and death among injured children. Cerebral damage may be due to secondary injuries to the brain and is potentially preventable. The need to preserve the spleen in children complicates the management of abdominal trauma. Although children usually have large cardiorespiratory reserves, they are likely to need airway control and ventilation with thoracic injuries. The psychologic effect of trauma may pose long-term problems and needs close follow-up.     

Identifying physiological measurements for medical monitoring: implications for autonomous health care in austere environments

In a patient who has lost a significant amount of blood, avoiding cardiovascular collapse and impending circulatory shock depends on the ability to maintain adequate arterial blood pressure in the presence of significant central hypovolemia. Our analysis of hemodynamic, autonomic, and metabolic data obtained from healthy human subjects exposed to progressive reduction in central blood volume and supported by data from trauma patients provide evidence to support the following conclusions: 1. Because of autonomically-mediated compensatory mechanisms, standard vital signs can remain unchanged or change too late, when cardiovascular collapse is imminent. 2. Currently proposed closed-loop resuscitation and oxygen delivery systems controlled by arterial blood pressure and SpO2 may prove inadequate for early intervention decision-support. 3. Continuous capture of PP, ECG R-wave amplitude, indices of HRV, cardiac BRS, and/or muscle PO2 could improve the sensitivity of closed-loop resuscitation and oxygen delivery by providing earlier indications of clinical status.     

Hypertonic saline enhances neutrophil elastase release through activation of P2 and A3 receptors

Hypertonic saline (HS) holds promise as a novel resuscitation fluid for the treatment of trauma patients because HS inhibits polymorphonuclear neutrophil (PMN) activation and thereby prevents host tissue damage and associated posttraumatic complications. However, depending on conditions of cell activation, HS can increase PMN degranulation, which could exacerbate tissue damage in trauma victims. The cellular mechanism by which HS increases degranulation is unknown. In the present study, we tested whether HS-induced ATP release from PMN and feedback via P1 and/or P2 receptors may be involved in the enhancement of degranulation by HS. We found that HS enhances elastase release and ERK and p38 MAPK activation when HS is added after activation of PMN with formyl peptide (fMLP) or phorbol ester (PMA). Agonists of P2 nucleotide and A3 adenosine receptors mimicked these enhancing effects of HS, whereas antagonists of A3 receptors or removal of extracellular ATP with apyrase diminished the response to HS. A1 adenosine receptor antagonists increased the enhancing effect of HS, whereas A1 receptor agonists inhibited elastase release. These data suggest that HS upregulates degranulation via ATP release and positive feedback through P2 and A3 receptors. We propose that these feedback mechanisms can serve as potential pharmacological targets to fine-tune the clinical effectiveness of HS resuscitation. resuscitation; inflammation; osmotic stimulation; nucleotide receptor signaling     

Liver cytokine production and ICAM-1 expression following bone fracture, tissue trauma, and hemorrhage in middle-aged mice

Although studies have indicated that hemorrhagic shock and resuscitation produces hepatic damage by mechanisms involving adhesion molecules in endothelial cells and hepatocytes, it is not known if there is any difference in the extent of hepatic damage following bone fracture, soft tissue trauma, and hemorrhage (Fx-TH) between young and middle-aged animals. To study this, young (6-8 wk) and middle-aged (approximately 12 mo) C3H/HeN male mice were subjected to a right lower leg fracture, soft tissue trauma, (i.e., midline laparotomy), and hemorrhage (blood withdrawal to decrease the blood pressure to 35 +/- 5 mmHg for 90 min) followed by resuscitation with four times the shed blood volume in the form of lactated Ringer solution. Mice were euthanized 24 h later, and liver tissues were harvested. Total bilirubin levels in the hepatocyte extract increased markedly following Fx-TH in both groups of mice; however, the increase in middle-aged mice was significantly higher compared with young mice. TNF-alpha and IL-6 levels in the hepatocyte extract following Fx-TH increased significantly in middle-aged mice but remained unchanged in young mice. IL-10 levels significantly decreased in middle-aged mice following Fx-TH but remained unchanged in young mice. Kupffer cells from middle-aged mice produced significantly higher IL-6 and IL-10 levels compared with young mice. Protein levels and mRNA expression of ICAM-1 in hepatocytes were also significantly higher in middle-aged mice compared with young mice following Fx-TH. These results collectively suggest that the extent of hepatic damage following Fx-TH is dependent on the age of the subject.     

限制性液体复苏对多发性骨折合并创伤失血性休克患者凝血功能、心肌损害指标及预后的影响

目的:探讨限制性液体复苏对多发性骨折合并创伤失血性休克患者凝血功能、心肌损害指标及预后的影响。方法:选取我院收治的多发性骨折合并创伤失血性休克患者77例,分为研究组(n=39)、对照组(n=38),对照组给予常规液体复苏,研究组给予限制性液体复苏,比较两组患者凝血功能、心肌损害指标、输液量、失血量、输血量、并发症发生率及病死率。结果:研究组的输液量、失血量、输血量均少于对照组(P0.05)。与复苏前相比,两组患者复苏1 h后凝血酶原时间(PT)、凝血活酶时间(APTT)、凝血酶时间(TT)均延长,且研究组长于对照组(P0.05);两组患者复苏1 h后肌酸激酶(CK)、肌酸激酶-同工酶(CK-MB)、肌钙蛋白T(CTnT)水平均下降,且研究组低于对照组(P0.05)。研究组复苏期间并发症发生率、病死率均低于对照组(P0.05)。结论:限制性液体复苏治疗多发性骨折合并创伤失血性休克患者,可改善患者凝血功能和预后,降低并发症发生率,同时还可减轻心肌损害。     

Effects of hypothermia and re-warming on the inflammatory response in a murine multiple hit model of trauma

INTRODUCTION: Although, hypothermia is a frequent event after trauma, it is unclear whether its beneficial or detrimental effects are more important. This study aims to quantify the effects of hypothermia and re-warming on the inflammatory response after fracture/hemorrhage and subsequent fracture stabilization with resuscitation. MATERIALS AND METHODS: Eighty-one male C57Bl/6 mice (aged 8-10 weeks, weighing 22.0+/-3.0 g) underwent femoral fracture and hemorrhage followed by resuscitation and splint fixation of the fracture. Animals were sacrificed 3h after induction of hemorrhage and fracture. Besides a sham group (n=6), four experimental groups were created: A: normothermia (n=12), B: hypothermia after trauma (n=21), C: re-warming after resuscitation and before stabilization (n=21), and D: hypothermia before trauma (n=21). Groups B-D were further subdivided into three subgroups according to the degree of hypothermia (subgroup 1: 35-33 degrees C, subgroup 2: 32.9-30.0 degrees C, and subgroup 3: 29.9-27.0 degrees C). Plasma cytokine (TNF-alpha, IL-6, and IL-10) and chemokine (MCP-1) concentrations were determined by ELISA, pulmonary permeability changes were quantified, and histological analysis of lung and liver tissues was performed. RESULTS: Normothermia resulted in a significantly increased early mortality rate. A significantly increased pro-inflammatory and decreased anti-inflammatory responses were also observed in normothermia as compared to hypothermia. The extent of these changes was most pronounced in the severe hypothermic group. Re-warming after mild hypothermia resulted in a pro-inflammatory response comparable to normothermia. CONCLUSION: Hypothermia has a beneficial effect on early survival after trauma, which appears to be independent of the level of hypothermia and re-warming. Re-warming, however, enhanced the pro-inflammatory response. Further studies with a longer posttraumatic observation period are required to investigate the long term effects of the hypothermia and re-warming-induced changes on the pro- and anti-inflammatory responses.     

角膜内皮细胞的检测、受损因素及治疗新进展

摘要：角膜内皮细胞(corneal endothelial cells,CECs)通过其屏障作用及离子泵功能维持角膜透明,但年龄、疾病及创伤等因素会使其功能有所降低,导致角膜失代偿、角膜水肿、大泡性角膜病变,甚至视力的丧失。因此,CECs可谓是角膜的"生命"。近年来,CECs的检测方法逐渐新增,并且不同检测指标具有不同意义;导致CECs受损的因素也有所增加,同时CECs损伤后的治疗也逐渐成为近年来的研究热点。早期发现CECs受损、明确病因并进行干预或治疗会减少CECs的损伤,对指导临床工作有重要的意义。本文主要对CECs检测方法及指标、损伤因素及其治疗的最新进展进行了综述。     

Examination of Physiological Function and Biochemical Disorders in a Rat Model of Prolonged Asphyxia-Induced Cardiac Arrest followed by Cardio Pulmonary Bypass Resuscitation

Background

Cardiac arrest induces whole body ischemia, which causes damage to multiple organs particularly the heart and the brain. There is clinical and preclinical evidence that neurological injury is responsible for high mortality and morbidity of patients even after successful cardiopulmonary resuscitation. A better understanding of the metabolic alterations in the brain during ischemia will enable the development of better targeted resuscitation protocols that repair the ischemic damage and minimize the additional damage caused by reperfusion.

Method

A validated whole body model of rodent arrest followed by resuscitation was utilized; animals were randomized into three groups: control, 30 minute asphyxial arrest, or 30 minutes asphyxial arrest followed by 60 min cardiopulmonary bypass (CPB) resuscitation. Blood gases and hemodynamics were monitored during the procedures. An untargeted metabolic survey of heart and brain tissues following cardiac arrest and after CPB resuscitation was conducted to better define the alterations associated with each condition.

Results

After 30 min cardiac arrest and 60 min CPB, the rats exhibited no observable brain function and weakened heart function in a physiological assessment. Heart and brain tissues harvested following 30 min ischemia had significant changes in the concentration of metabolites in lipid and carbohydrate metabolism. In addition, the brain had increased lysophospholipid content. CPB resuscitation significantly normalized metabolite concentrations in the heart tissue, but not in the brain tissue.

Conclusion

The observation that metabolic alterations are seen primarily during cardiac arrest suggests that the events of ischemia are the major cause of neurological damage in our rat model of asphyxia-CPB resuscitation. Impaired glycolysis and increased lysophospholipids observed only in the brain suggest that altered energy metabolism and phospholipid degradation may be a central mechanism in unresuscitatable brain damage.     

Tailored treatment strategies for cancer patients during COVID-19 pandemic

The global pandemic of respiratory disease caused by the novel human coronavirus (SARS-CoV-2) has caused indefinite global distress, uncertainty, and disturbance. This pandemic has had direct and indirect impacts for the healthcare systems across the world, but certain subgroups of patients have been particularly affected. Among these groups are patients with cancer, who as a result of their immunosuppressed status either from the disease itself or as a consequence of treatment, are at increased risk of severe COVID-19 infection and complications. The pandemic has also led to limited resources as medical services have been primarily directed to emergency care. In this context, physicians and healthcare providers have had to balance the importance of continuing treatment of cancer patients with the risk of virus infection.In this review, we outline the treatment strategies for cancer patients during this pandemic, focusing on tailored treatment in this challenging situation of varying risks and benefits.     

损伤控制外科在严重胸外伤为主的全身多发伤救治中的应用

目的:探讨损伤控制外科(DCS)在严重胸外伤为主的全身多发伤救治中应用的临床效果。方法:2010年1月至2012年6月收治的57例患者采用早期全面治疗(ETC组),2012年7月至2013年12月收治的57例患者采用DCS理论救治(DCS组)。比较两组相关生理指标恢复情况及并发症的发生情况。结果:与ETC组比较,DCS组乳酸清除时间、体温恢复时间、PT和APTT恢复时间、住院时间、ICU治疗时间明显缩短,出血量明显减少(P0.05);DCS组腹腔感染、ARDS、应激性溃疡的发生率及死亡率均较ETC组明显降低(P0.05)。结论:严重胸外伤为主的全身多发伤救治中应用DCS理论可明显改善患者生理指标恢复,减少并发症,提高救治成功率。     

A Four-Compartment Metabolomics Analysis of the Liver,Muscle, Serum,and Urine Response to Polytrauma with Hemorrhagic Shock following Carbohydrate Prefeed

Objective

Hemorrhagic shock accompanied by injury represents a major physiologic stress. Fasted animals are often used to study hemorrhagic shock (with injury). A fasted state is not guaranteed in the general human population. The objective of this study was to determine if fed animals would exhibit a different metabolic profile in response to hemorrhagic shock with trauma when compared to fasted animals.

Methods

Proton (1H) NMR spectroscopy was used to determine concentrations of metabolites from four different compartments (liver, muscle, serum, urine) taken at defined time points throughout shock/injury and resuscitation. PLS-DA was performed and VIP lists established for baseline, shock and resuscitation (10 metabolites for each compartment at each time interval) on metabolomics data from surviving animals.

Results

Fed status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The death rate for CPF animals is higher than FS animals (47 vs 28%). The majority of deaths occur post-resuscitation suggesting reperfusion injury. The metabolomics response to shock reflects priorities evident at baseline. FS animals raise the baseline degree of proteolysis to provide additional amino acids for energy production while CPF animals rely on both glucose and, to a lesser extent, amino acids. During early resuscitation levels of metabolites associated with energy production drop, suggesting diminished demand.

Conclusions

Feeding status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The response to shock reflects metabolic priorities at baseline.     

Bone marrow edema and osteitis in rheumatoid arthritis: the imaging perspective

Magnetic resonance imaging bone marrow edema is an imaging feature that has been described in many conditions, including osteomyelitis, overuse syndromes, avascular necrosis, trauma, and inflammatory arthritides. In rheumatoid arthritis (RA), bone edema has special significance as it has been shown to be a common and widespread lesion that is often apparent at the hands and wrists but has also been described elsewhere, including the feet. It may occur in early or late disease and has been shown in several large cohort studies to have major negative implications for prognosis. It is the strongest predictor of erosive progression yet to be identified and characteristically occurs in those patients with the most aggressive and potentially disabling disease. In patients with undifferentiated arthritis, bone edema also predicts progression to criteria-positive RA, both independently and to a greater extent when combined with anti-cyclic citrullinated peptide status or rheumatoid factor positivity. Its histological correlate in the late stages of RA has been shown to be osteitis, in which the bone marrow beneath the joint is invaded by an inflammatory and vascular lymphoplasmacytic infiltrate. This lies adjacent to trabecular bone, where increased numbers of osteoclasts have been observed within resorption lacunae, suggesting a mechanistic link between inflammation and erosive bone damage. This could lead to erosion both of the overlying cortex, leading to classic radiographic rheumatoid erosions, and of local trabecular bone, possibly contributing to periarticular osteopenia and cyst formation. In addition to synovitis, osteitis is now regarded as a major rheumatoid lesion that is responsive to therapeutic intervention.     

Hypoxia in patients with acute hemiplegia.

Sixteen patients with an early dense hemiplegia due to cerebrovascular accidents were shown to have a greater degree of hypoxia than 16 matched control patients. The patients with hemiplegia had a reflex compensatory fall in arterial carbon dioxide tensions (PaCO2) with possible reduction in cerebral blood flow. Oxygen treatment led to an increase in PaCO2 in the patients with hemiplegia, but the increase in oxygen tensions in these patients was significantly less than that in the control group, suggesting increased pulmonary shunting as the cause for the hypoxia. Oxygen treatment may improve cerebral blood flow and oxygenation and have a useful role in the early management of patients with a dense hemiplegia.     

Prevention of depression and anxiety in adolescents: A randomized controlled trial testing the efficacy and mechanisms of Internet-based self-help problem-solving therapy

Background

Fractures of the long bones and femur fractures in particular are common in multiple trauma patients, but the optimal management of femur fractures in these patients is not yet resolved. Although there is a trend towards the concept of "Damage Control Orthopedics" (DCO) in the management of multiple trauma patients with long bone fractures as reflected by a significant increase in primary external fixation of femur fractures, current literature is insufficient. Thus, in the era of "evidence-based medicine", there is the need for a more specific, clarifying trial.

Methods/Design

The trial is designed as a randomized controlled open-label multicenter study. Multiple trauma patients with femur shaft fractures and a calculated probability of death between 20 and 60% will be randomized to either temporary fracture fixation with fixateur externe and defined secondary definitive treatment (DCO) or primary reamed nailing (early total care). The primary objective is to reduce the extent of organ failure as measured by the maximum sepsis-related organ failure assessment (SOFA) score.

Discussion

The Damage Control Study is the first to evaluate the risk adapted damage control orthopedic surgery concept of femur shaft fractures in multiple trauma patients in a randomized controlled design. The trial investigates the differences in clinical outcome of two currently accepted different ways of treating multiple trauma patients with femoral shaft fractures. This study will help to answer the question whether the "early total care" or the ?damage control” concept is associated with better outcome.

Trial registration

Current Controlled Trials ISRCTN10321620     

Role of thromboxane in producing portal hypertension following trauma-hemorrhage

Thromboxane A2 (TXA2) and endothelin-1 (ET-1) have been proposed as the important vasoconstrictors that increase portal venous resistance in paracrine or autocrine fashion. We hypothesized that the hepatic damage following trauma-hemorrhage (T-H) is induced by the impaired hepatic circulation due to the increased production of vasoconstrictors such as ET-1 and TXA2 by the liver. To test this, male Sprague-Dawley rats (n = 6/group) were subjected to trauma (i.e., midline laparotomy) and hemorrhage (35-40 mmHg for 90 min followed by fluid resuscitation) or sham operation. At 2 or 5 h after the end of resuscitation, the liver was isolated and perfused and portal inflow pressure, bile flow, and release of ET-1 and thromboxane B2 (TXB2; a stable metabolite of TXA2) into the perfusate were measured. The level of portal pressure was higher at 5 h following T-H compared with 2 h after T-H and sham. The portal pressure was inversely correlated to the amount of bile production. Furthermore, the bile flow was significantly correlated to the hepatic damage as evidenced by release of lactate dehydrogenase into the perfusate. The level of ET-1 at 5 h following T-H in the perfusate after 30 min of recirculation did not show any difference from sham. However, the levels of TXB2 in the T-H group were significantly higher than those in sham at that interval. These results indicate that the increased release of TXA2 but not ET-1 following T-H might be responsible for producing the increased portal resistance, decreased bile production, and hepatic damage.     

ATP-MgCl2 restores renal microcirculation following trauma and severe hemorrhage.

Although ATP-MgCl2 enhances the recovery of renal function after ischemia and reperfusion, it is not known whether this agent has any beneficial effects on renal microcirculation and function in a nonheparinized model of trauma and severe hemorrhage. To study this, a midline laparotomy was performed (i.e., trauma induced) and the rats were bled to and maintained at a mean arterial pressure of 40 mmHg (1 mmHg = 133.32 Pa) until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate (RL) solution. Animals were then resuscitated with 4 times the volume of the shed blood in the form of RL. ATP-MgCl2, 50 mumol/kg body weight, or an equivalent volume of saline, was infused intravenously during and following resuscitation. Renal microcirculation was examined by using colloidal carbon infusion and laser Doppler flow-metry. Glomerular filtration rate (GFR) was assessed with [3H]inulin clearance and cardiac output (CO) was determined by dye dilution technique. The results indicate that the depressed renal microcirculation following hemorrhage and resuscitation was restored by ATP-MgCl2 treatment. GFR was significantly higher in ATP-MgCl2-treated than saline-treated rats. ATP-MgCl2 also increased urine output, restored the decreased CO, and prevented the occurrence of renal edema after hemorrhage and resuscitation. Thus, ATP-MgCl2 appears to be a useful adjunct to crystalloid resuscitation following trauma and severe hemorrhagic shock even in the absence of blood resuscitation.     

Oxidative DNA damage and plasma antioxidant capacity in type 2 diabetic patients with good and poor glycaemic control

Diabetes mellitus is a complex metabolic disorder characterized by a disturbance in glucose metabolism. Recent evidence suggests that increased oxidative damage as well as reduction in antioxidant capacity could be related to the complications in patients with type 2 diabetes. The aim of this study was to measure plasma antioxidant status in type 2 diabetic patients with good and poor glycaemic control and its relationship with oxidative DNA damage. Thirty-nine type 2 diabetic patients and eighteen healthy subjects were recruited for this study. We found that diabetic patients had slightly, but not significantly lower antioxidant capacity, measured with the "ferric reducing ability of plasma" (FRAP) assay, than healthy subjects. On the contrary, oxidative DNA damage (measured by the Comet assay) in leukocytes obtained from diabetic patients was significantly higher compared to healthy subjects. Taking into account glucose control, we found that the FRAP level was significantly (p<0.05) lower in diabetic subjects with poor glycaemic control than healthy subjects, while patients with good glycaemic control had FRAP values similar to controls. We also observed an unexpected positive correlation between FRAP values and oxidative DNA damage in diabetic patients; moreover, a positive correlation was found between FRAP and glucose level or HbA(1c) in patients with poor glycaemic control. In conclusion, our results confirm that patients with type 2 diabetes have a higher oxidative DNA damage than healthy subjects and that plasma antioxidant capacity is significantly lower only in patients with poor glycaemic control, moreover, in these patients FRAP values are positively correlated with glycaemic levels and HbA(1c). These observations indicate that a compensatory increase of the antioxidant status is induced as a response to free radical overproduction in type 2 diabetes. Therefore, the addition of antioxidant supplements to the current pharmacological treatment could have potentially beneficial effects in diabetic patients with poor glycaemic control.     

Molecular mechanisms of inflammation and tissue injury after major trauma-is complement the "bad guy"?

Trauma represents the leading cause of death among young people in industrialized countries. Recent clinical and experimental studies have brought increasing evidence for activation of the innate immune system in contributing to the pathogenesis of trauma-induced sequelae and adverse outcome. As the "first line of defense", the complement system represents a potent effector arm of innate immunity, and has been implicated in mediating the early posttraumatic inflammatory response. Despite its generic beneficial functions, including pathogen elimination and immediate response to danger signals, complement activation may exert detrimental effects after trauma, in terms of mounting an "innocent bystander" attack on host tissue. Posttraumatic ischemia/reperfusion injuries represent the classic entity of complement-mediated tissue damage, adding to the "antigenic load" by exacerbation of local and systemic inflammation and release of toxic mediators. These pathophysiological sequelae have been shown to sustain the systemic inflammatory response syndrome after major trauma, and can ultimately contribute to remote organ injury and death. Numerous experimental models have been designed in recent years with the aim of mimicking the inflammatory reaction after trauma and to allow the testing of new pharmacological approaches, including the emergent concept of site-targeted complement inhibition. The present review provides an overview on the current understanding of the cellular and molecular mechanisms of complement activation after major trauma, with an emphasis of emerging therapeutic concepts which may provide the rationale for a "bench-to-bedside" approach in the design of future pharmacological strategies.