COMPLEMENT ACTIVATION IN THE CENTRAL-NERVOUS-SYSTEM FOLLOWING BLOOD-BRAIN-BARRIER DAMAGE IN MAN

The central nervous system (CNS) is virtually isolated from circulatin g 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 pr oduce an abnormal blood-brain/cerebrospinal fluid (blood-brain/CSF) pe rmeability allowing C protein extravasation, we investigated if C acti vation occurs in CSF in vitro and in CNS in vivo during subarachnoid h emorrhage (SAH) or brain infarction. After SAH (n = 15), the terminal complement complex (TCC) concentration on days 0 to 2 was higher in th e 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 d ays 7 to 10). Incubation of normal human CSF with serum in vitro also activated the terminal C pathway. In 10 fatal ischemic brain infarctio ns, immunohistochemical techniques demonstrated neuronal fragment-asso ciated deposition of C9 accompanied by neutrophil infiltration. We con clude that the C system becomes activated intrathecally in SAH and foc ally in the brain parenchyma in ischemic stroke. By promoting chemotax is and vascular perturbation, C activation may instigate nonimmune inf lammation and aggravate CNS damage in diseases associated with plasma extravasation.