The anaphylatoxins C3a and C5a have been reported to exert both protective and detrimental effects in the central nervous system (82, 83) . It is noteworthy that many cells of the central nervous system are more susceptible to a complement attack, since they lack important complement regulators such as CD59 (84) . Complement products were demonstrated to be dramatically upregulated in models of cerebral ischemia in rats (85) , and evidence for deposition of C3d and C9 after experimental cerebral contusion was found (86) . In agreement with these experimental findings, systemic complement activation has been shown in stroke patients (87) . A negative role for complement has been proposed in traumatic brain injury, since systemic depletion of complement by infusion of the cobra venom factor improved blood flow and neurological function and reduced cerebral edema during experimental intracerebral hemorrhage (88, 89) . Moreover, C1 deficiency (90) and complement inhibition by infusion of the C1 inhibitor revealed some neuroprotective effects (91, 92) . In contradiction to these results for traumatic/ischemic injuries, C1q has a strong neuroprotective effect in neu-rodegenerative diseases (93) . Traumatic brain injury induces C5aR upregulation in an experimental model in rats with enhanced C5a serum levels for >1 week. The functional consequences of traumatic brain injury-induced systemic C5a generation have still to be elucidated (94) .