title: Intrathecal levels of complement-derived soluble membrane attack complex (sC5b-9) correlate with blood-brain barrier dysfunction in patients with traumatic brain injury.
abstract: It has become evident in recent years that intracranial inflammation after traumatic brain injury (TBI) is, at least in part, mediated by activation of the complement system. However, most conclusions have been drawn from experimental studies, and the intrathecal activation of the complement cascade after TBI has not yet been demonstrated in humans. In the present study, we analyzed the levels of the soluble terminal complement complex sC5b-9 by ELISA in ventricular cerebrospinal fluid (CSF) of patients with severe TBI (n = 11) for up to 10 days after trauma. The mean sC5b-9 levels in CSF were significantly elevated in 10 of 11 TBI patients compared to control CSF from subjects without trauma or inflammatory neurological disease (n = 12; p < 0.001). In some patients, the maximal sC5b-9 concentrations were up to 1,800-fold higher than in control CSF. The analysis of the extent of posttraumatic blood-brain barrier (BBB) dysfunction, as determined by CSF/serum albumin quotient (Q(A)), revealed that patients with a moderate to severe BBB impairment (mean Q(A) > 0.01) had significantly higher intrathecal sC5b-9 levels as compared to patients with normal BBB function (mean Q(A) < 0.007; p < 0.0001). In addition, a significant correlation between the individual daily Q(A) values and the corresponding sC5b-9 CSF levels was detected in 8 of 11 patients (r = 0.72-0.998; p < 0.05). These data demonstrate for the first time that terminal pathway complement activation occurs after head injury and suggest a possible pathophysiological role of complement with regard to posttraumatic BBB dysfunction.
authors.affiliation: Department of Surgery, University Hospital, Zurich, Switzerland. philip.stahel@ukbf.fu-berlin.de
authors.forename: P F
authors.initials: PF
authors.lastname: Stahel
authors.forename: M C
authors.initials: MC
authors.lastname: Morganti-Kossmann
authors.forename: D
authors.initials: D
authors.lastname: Perez
authors.forename: C
authors.initials: C
authors.lastname: Redaelli
authors.forename: B
authors.initials: B
authors.lastname: Gloor
authors.forename: O
authors.initials: O
authors.lastname: Trentz
authors.forename: T
authors.initials: T
authors.lastname: Kossmann
mesh_terms: D000293:Adolescent; D000328:Adult; D001812:Blood-Brain Barrier / Q000276:immunology*; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000276:immunology* / Q000503:physiopathology; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000134:cerebrospinal fluid*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; C047610:SC5b-9 protein complex; D012709:Serum Albumin; D003165:Complement System Proteins