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Nd leukocyte infiltration in the subarachnoid space and cerebral PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/22026160 parenchyma [84]. In addition, MAC injection into hippocampus evoked seizures and neurocytoxic effects in rats [85]. Local MAC deposition in the injured brain was demonstrated in experimental models [86] and in injured human brains [87]. The complement regulatory molecule CD59 represents the main controlling molecule of MAC formation and an essential protector from neuronal cell injury after complement activation [51,88]. Neurons express CD59 constitutively, as a protective mechanism from autologous "innocent bystander" cell lysis after complement activation in the brain [51,89]. However, the posttraumatic activation of phosphatidyl-inositol-specific phospholipase C (PI-PLC) after traumatic brain injury renders neurons vulnerable to MAC-mediated lysis PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/21715270 by shedding of the glycosyl-phosphatidyl-inositol (GPI)-anchored glycoprotein CD59 from neuronal membranes [88,90]. A recent experimental study on closed head injury in mice lacking the gene for Cd59a (CD59a-/-) revealed increased susceptibility to brain injury in CD59a-/- mice, compared to wild-type littermates [88]. In fact, head-injured CD59a -/- mice showed increased neuronal cell death in tissue sections assessed by TUNEL histochemistry, in conjunction with elevated serum levels of neuron specific enolase (NSE), an indirect marker of neuronal injury [88]. These data corroborate the crucial role of the complement regulatory molecule CD59 in protecting neurons from complement-mediated lysis, and emphasize the impact of the terminal complement pathway in contributing to the pathophysiology of delayed neuronal cell death after TBI. Until present, there is a lack of specific pharmacological therapy designed to avoid induction of secondary brain injuries and delayed neuronal cell death [91]. There have been some significant advances in the field of therapeutic complement inhibitor development, in recent years [43,74,92-94]. While some of these inhibitors have been successfully tested in experimental head injury models (Table 1) [67,68,71,80], the "bench-tobedside" extrapolation to clinical applications in headinjured patients has yet to be accomplished [91].Chest trauma and acute lung injurySevere blunt chest trauma with associated pulmonary contusions is characterized by a robust inflammatory reaction which can result in exacerbated lung injury, acute respiratory distress syndrome (ARDS), multiple organ failure, and death [95-99]. Activation of alveolar macrophages and recruitment of neutrophils 2-Chloro-3-methoxyaniline into the interstitial and alveolar compartments are followed by the release of an arsenal ofproteinases and oxidants causing leakage of the pulmonary microvasculature and destruction of the alveolar epithelium [100-103]. Various experimental models of lung injury could yield important insights into the critical role of complement activation products, particularly anaphylatoxin C5a, in the pathophysiology of trauma-induced lung inflammation and progressive alveolar injury [28,104-106]. tert-Butyl (7-bromoheptyl)carbamate Elevated levels of C5a have been described in broncheoalveolar fluid samples from patients with acute lung injury [28,107,108]. When C5a was applied intratracheally in rats exposed to an IgG immune complex model, increased intrapulmonary generation of chemokines, accumulation of neutrophils and changes in vascular permeability could be detected [106]. The protective effects of anti-C5a were further corroborated by the observation that the antibody also su.