title: Complement activation in the central nervous system following blood-brain barrier damage in man.
abstract: The central nervous system (CNS) is virtually isolated from circulating immunological factors such as complement (C), an important mediator of humoral immunity and inflammation. In circulation, C is constantly inhibited to prevent attack on host cells. Since a host of diseases produce an abnormal blood-brain/cerebrospinal fluid (blood-brain/CSF) permeability allowing C protein extravasation, we investigated if C activation occurs in CSF in vitro and in CNS in vivo during subarachnoid hemorrhage (SAH) or brain infarction. After SAH (n = 15), the terminal complement complex (TCC) concentration on days 0 to 2 was higher in the CSF, 210 +/- 61 ng/ml, than in the plasma, 63 +/- 17 ng/ml, but null in the CSF of controls (n = 8) or patients with an ischemic stroke (n = 7). TCC was eliminated from the CSF after SAH (24 +/- 10 ng/ml on days 7 to 10). Incubation of normal human CSF with serum in vitro also activated the terminal C pathway. In 10 fatal ischemic brain infarctions, immunohistochemical techniques demonstrated neuronal fragment-associated deposition of C9 accompanied by neutrophil infiltration. We conclude that the C system becomes activated intrathecally in SAH and focally in the brain parenchyma in ischemic stroke. By promoting chemotaxis and vascular perturbation, C activation may instigate nonimmune inflammation and aggravate CNS damage in diseases associated with plasma extravasation.
authors.affiliation: Department of Neurology, University of Helsinki, Finland.
authors.forename: P J
authors.initials: PJ
authors.lastname: Lindsberg
authors.forename: J
authors.initials: J
authors.lastname: Ohman
authors.forename: T
authors.initials: T
authors.lastname: Lehto
authors.forename: M L
authors.initials: ML
authors.lastname: Karjalainen-Lindsberg
authors.forename: A
authors.initials: A
authors.lastname: Paetau
authors.forename: T
authors.initials: T
authors.lastname: Wuorimaa
authors.forename: O
authors.initials: O
authors.lastname: Carpén
authors.forename: M
authors.initials: M
authors.lastname: Kaste
authors.forename: S
authors.initials: S
authors.lastname: Meri
mesh_terms: D000328:Adult; D017542:Aneurysm, Ruptured / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001623:Betamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D001812:Blood-Brain Barrier; D001921:Brain / Q000503:physiopathology / Q000648:ultrastructure; D002633:Chemotaxis; D003167:Complement Activation / Q000502:physiology*; D015938:Complement Membrane Attack Complex / Q000502:physiology*; D004492:Edetic Acid; D005119:Extravasation of Diagnostic and Therapeutic Materials; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D009553:Nimodipine / Q000008:administration & dosage / Q000627:therapeutic use; D013345:Subarachnoid Hemorrhage / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D014057:Tomography, X-Ray Computed; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D015938:Complement Membrane Attack Complex; D014665:Vasodilator Agents; D009553:Nimodipine; D001623:Betamethasone; D004492:Edetic Acid