[The relevance of the inflammatory response in the injured brain]. / Die Bedeutung der posttraumatischen Entzündungsreaktion im verletzten Gehirn.

Research efforts in recent years have defined traumatic brain injury (TBI) as a predominantly immunological and inflammatory disorder. This perception is based on the fact that the overwhelming neuroinflammatory response in the injured brain contributes to the development of posttraumatic edema and to neuropathological sequelae which are, in large part, responsible for the adverse outcome. While the "key" mediators of neuroinflammation, such as the cytokine cascade and the complement system, have been clearly defined by studies in experimental TBI models, their exact pathways of interaction and pathophysiological implications remain to be further elucidated. This lack of knowledge is partially due to the concept of a "dual role" of the neuroinflammatory response after TBI. This notion implies that specific inflammatory molecules may mediate diverse functions depending on their local concentration and kinetics of expression in the injured brain. The inflammation-induced effects range from beneficial aspects of neuroprotection to detrimental neurotoxicity. The lack of success in pushing anti-inflammatory therapeutic concepts from"bench to bedside" for patients with severe TBI strengthens the further need for advances in basic research on the molecular aspects of the neuroinflammatory network in the injured brain. The present review summarizes the current knowledge from experimental studies in this field of research and discusses potential future targets of investigation.

Erythropoietin is neuroprotective, improves functional recovery, and reduces neuronal apoptosis and inflammation in a rodent model of experimental closed head injury.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young people in industrialized countries. Although various anti-inflammatory and antiapoptotic modalities have shown neuroprotective effects in experimental models of TBI, to date, no specific pharmacological agent aimed at blocking the progression of secondary brain damage has been approved for clinical use. Erythropoietin (Epo) belongs to the cytokine superfamily and has traditionally been viewed as a hematopoiesis-regulating hormone. The newly discovered neuroprotective properties of Epo lead us to investigate its effect in TBI in a mouse model of closed head injury. Recombinant human erythropoietin (rhEpo) was injected at 1 and 24 h after TBI, and the effect on recovery of motor and cognitive functions, tissue inflammation, axonal degeneration, and apoptosis was evaluated up to 14 days. Motor deficits were lower, cognitive function was restored faster, and less apoptotic neurons and caspase-3 expression were found in rhEpo-treated as compared with vehicle-treated animals (P<0.05). Axons at the trauma area in rhEpo-treated mice were relatively well preserved compared with controls (shown by their density; P<0.01). Immunohistochemical analysis revealed a reduced activation of glial cells by staining for GFAP and complement receptor type 3 (CD11b/CD18) in the injured hemisphere of Epo- vs. vehicle-treated animals. We propose that further studies on Epo in TBI should be conducted in order to consider it as a novel therapy for TBI.

Predictive value of complement activation fragments C3a and sC5b-9 for development of severe disease in patients with acute pancreatitis.

BACKGROUND: Complement activation has been shown to occur in patients with acute pancreatitis. However, the diagnostic potential of complement activation products in plasma for predicting severe disease remains unclear to date. METHODS: The daily levels of the complement anaphylatoxin C3a and the soluble terminal complement complex sC5b-9 were determined by ELISA in plasma of patients with mild (n = 16) or severe (n = 14) acute pancreatitis during the first week after onset of symptoms, and in healthy control subjects (n = 14). RESULTS: Both C3a and sC5b-9 were significantly elevated during the first 7 days in plasma of patients with severe acute pancreatitis (C3a: 459.3 +/- 407.5 ng/mL (mean +/- s); sC5b-9: 617.9 +/- 297.7 ng/mL), as compared to patients with mild disease (C3a: 172 +/- 149.5 ng/mL; sC5b-9: 306.7 +/- 167.3 ng/mL) or controls (C3a: 102.3 +/- 19.7 ng/mL; sC5b-9: 40.64 +/- 19.7 ng/mL; P < 0.001, repeated measures ANOVA). The analysis of both parameters in combination during the first week after onset of symptoms revealed a high sensitivity (0.93) and specificity (0.88) as well as high negative and positive predictive values (0.93 and 0.87, respectively) with an odds ratio of 91.0 for the development of pancreatic necrosis (P < 0.0001, Fisher exact test). CONCLUSION: In patients with acute pancreatitis, the plasma levels of complement C3a and sC5b-9 measured daily during the first week after onset of symptoms represent highly specific and sensitive parameters for the prediction of severe acute pancreatitis.