Complement activation in the central nervous system following blood-brain barrier damage in man.
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.
Lindsberg
P J
PJ
Department of Neurology, University of Helsinki, Finland.
Ohman
J
J
Lehto
T
T
Karjalainen-Lindsberg
M L
ML
Paetau
A
A
Wuorimaa
T
T
Carpén
O
O
Kaste
M
M
Meri
S
S
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
D000893:Anti-Inflammatory Agents; D015938:Complement Membrane Attack Complex; D014665:Vasodilator Agents; D009553:Nimodipine; D001623:Betamethasone; D004492:Edetic Acid