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


METHODS
Twenty 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 (Q (A)).


RESULTS
Following 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.


CONCLUSIONS
This 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.
Bellander
Bo-Michael
BM
Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden. bo-michael.bellander@karolinska.se
Olafsson
Ingvar Hakon
IH
Ghatan
Per Hamid
PH
Bro Skejo
Hanne Pernille
HP
Hansson
Lars-Olof
LO
Wanecek
Mikael
M
Svensson
Mikael A
MA
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000201:enzymology; D003167:Complement Activation / Q000502:physiology*; D015938:Complement Membrane Attack Complex / Q000134:cerebrospinal fluid / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D055815:Young Adult
D015415:Biomarkers; D015938:Complement Membrane Attack Complex; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D010751:Phosphopyruvate Hydratase