Secondary insults following traumatic brain injury enhance complement activation in the human brain and release of the tissue damage marker S100B

Abstract

ObjectComplement activation has been suggested to play a role in the development of secondary injuries following traumatic brain injury (TBI). The present study was initiated in order to analyze complement activation in relation to the primary brain injury and to secondary insults, frequently occurring following TBI.MethodsTwenty patients suffering from severe TBI (Glasgow coma score ≤8) were included in the study. The “membrane attack complex,” C5b9, which is the cytolytic end product of the complement system was analyzed in cerebrospinal fluid (CSF). The degree of brain tissue damage was assessed using the release of S100B and neuron-specific enolase (NSE) to the CSF and blood. The blood–brain barrier was assessed using the CSF/serum quotient of albumin (QA).ResultsFollowing impact, initial peaks (0–48 h) of C5b9, S100B, and NSE with a concomitant loss of integrity of the blood–brain barrier were observed. Secondary insults at the intensive care unit were monitored. Severe secondary insults were paralleled by a more pronounced complement activation (C5b9 in CSF) as well as increased levels of S100B (measured in CSF), but not with NSE.ConclusionThis human study indicates that complement activation in the brain is triggered not only by the impact of trauma per se but also by the amount of secondary insults that frequently occur at the scene of accident as well as during treatment in the neurointensive care unit. Complement activation and in particular the end product C5b9 may in turn contribute to additional secondary brain injuries by its membrane destructive properties.

Challenging the Role of Adaptive Immunity in Neurotrauma: Rag1−/− Mice Lacking Mature B and T Cells Do Not Show Neuroprotection after Closed Head Injury

“…3). These findings support the notion that complement is activated after TBI (Bellander et al, 2011;Stahel et al, 2001), and imply a crosslink between innate and adaptive immunity, as it relates to attenuated C3a levels observed in Rag1 -/ -mice. One of the common links in this network of innate and adaptive immune responses may be represented by pathogenic natural antibodies produced by B cells (Fleming, 2006;Holers, 2005;Holers and Kulik, 2007).…”

“…The complement system has been identified as an important effector arm of the innate immune system which mediates the hyperinflammatory response after severe head injury, leading to a breakdown of the blood-brain barrier (BBB), development of cerebral edema, and induction of delayed neuronal cell death (Bellander et al, 2010(Bellander et al, ,2011Gasque, 2004;Stahel and Barnum, 2006;Stahel et al, 1998Stahel et al, ,2001van Beek et al, 2003). Historically, the classic dogma of ''immune privilege'' in the brain sustained the long-standing notion that adaptive immune responses are not involved in the pathophysiology of TBI, mainly due to the absence of B and T lymphocytes in the central nervous system (CNS; Galea et al, 2007a;Hazlett and Hendricks, 2010;Perry, 1998;Rhodes, 2011).…”

Time-Dependent Changes in Serum Level of Protein Biomarkers after Focal Traumatic Brain Injury

“…Increased levels of S100B in TBI patients have been correlated to secondary events [19,40]. A second, delayed peak in serum S100B levels has been found indicative of poor outcome after severe TBI [41].…”

“…It is much dependent on collecting time following trauma and increased serum S100B levels have been found in other conditions and S100B can be of extracranial origin [45,46]. Elevated serum levels of S100B have been shown to correlate with BBB dysfunction albeit but not at late post-injury time point [40,47].…”

Neuromarkeriai

“…Tas pats Olivecrona su bendraautoriais nustatė, kad nėra statistiškai reikšmingos koreliacijos tarp serumo S100B koncentracijos ir GIS (10). Bellander su kolegomis nerado statistiškai reikšmingos koreliacijos nei tarp serumo, nei tarp CNS likvoro S100B koncentracijų su GIS (12). Todėl autoriai teigia, kad S100B nėra vertingas prognostinis veiksnys baigtims po sunkios CNS traumos.…”