Premium
Complement activation in the central nervous system following blood–brain barrier damage in man
Author(s) -
Lindsberg Perttu J.,
Öhman Juha,
Lehto Timo,
Wuorimaa Tomi,
Meri Seppo,
KarjalainenLindsberg MarjaLiisa,
Paetau Anders,
Carpén Olli,
Kaste Markku
Publication year - 1996
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410400408
Subject(s) - extravasation , cerebrospinal fluid , blood–brain barrier , central nervous system , complement system , inflammation , medicine , parenchyma , vascular permeability , meninges , immunology , pathology , immune system , endocrinology
The central nervous system (CNS) is virtually isolated from circulating immunological factors such as complment (C), an important mediator of humoral immunity and inflammation. In circulation, C i 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 hermorrhage (SAH) or brain infrarction. 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 ischmemic brain infrarctions, 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.