Intrathecal Levels of Complement-Derived Soluble Membrane Attack Complex (sC5b-9) Correlate with Blood–Brain Barrier Dysfunction in Patients with Traumatic Brain Injury

• Published in: Journal of neurotrauma Vol. 18; no. 8; pp. 773 - 781
• Main Authors: Stahel, Philip F., Morganti-Kossmann, Maria C., Perez, Daniel, Redaelli, Claudio, Gloor, Beat, Trentz, Otmar, Kossmann, Thomas
• Format: Journal Article
• Language: English
• Published: Larchmont, NY Liebert 01.08.2001; Mary Ann Liebert, Inc
• Subjects: Adolescent; Adult; Alzheimer's disease; Biological and medical sciences; Blood-Brain Barrier - immunology; Brain Injuries - cerebrospinal fluid; Brain Injuries - immunology; Brain Injuries - physiopathology; Catheters; Cell death; Cerebrospinal fluid; Complement Membrane Attack Complex; Complement System Proteins - cerebrospinal fluid; Disease; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins - cerebrospinal fluid; Head injuries; Humans; Injuries of the nervous system and the skull. Diseases due to physical agents; Male; Medical sciences; Membranes; Middle Aged; Serum Albumin - metabolism; Surgery; Trauma; Traumas. Diseases due to physical agents; Traumatic brain injury; Switzerland; Human; Nervous system diseases; Pathophysiology; C5b Complement; Craniocerebral; Diseases of the osteoarticular system; Albumin; Cerebral ventricle; Cerebrospinal fluid; Blood brain barrier; Trauma; Cerebral disorder; Central nervous system disease; Skull disease; Adult; Complement C9
• ISSN: 0897-7151; 1557-9042
• DOI: 10.1089/089771501316919139

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.