Table 1.

Insights from experimental complement inhibition based on genetically engineered mice and pharmacological approaches in models of traumatic brain injury (TBI).

Complement inhibitor/mouse strain	Inhibited complement molecule	Affected complement pathway	Inhibition-induced effects	Reference
C3-/- mice	C3	Classical, alternative, lectin	Reduction of neutrophil extravasation, injury sizes and chemokine expression.	Sewell et al., 2004 [67]
C4-/- mice	C4	Classical, lectin	Decrease of motor deficits and brain lesion size.	You et al., 2007 [81]
Factor B-/- mice, anti-factor B monoclonal Ab	Factor B	Alternative	Attenuation of cerebral tissue damage and neuronal apoptosis, upregulation of anti-apoptotic mediators, down-regulation of pro-apoptotic markers.	Leinhase et al., 2006, 2007 [79,80]
CD59a-/- mice	CD59a	Terminal	Exacerbated tissue injury in CD59a-deficient mice, implying MAC-mediated secondary neuronal cell death.	Stahel et al., 2009 [88]
C1-INH	C1r/s, MASPs, C3b	Classical	Reduction of motor deficits, cognitive dysfunction and contusion volume.	Longhi et al., 2009 [59]
sCR1	C3 convertases	Classical, alternative, lectin	Reduction of neutrophil accumulation in the brain.	Kaczorowski et al., 1995 [68]
Crry-Ig, GFAP-sCrry mice	C3 convertases	Classical, altenative, lectin	Neuroprotection with improved neurological scores and decreased tissue injury and blood-brain barrier dysfunction.	Leinhase et al., 2006 [71] Rancan et al., 2003 [70]
VCP	C3b, C4b, C3 convertases	Classical, alternative, lectin	Improvement of sensorimotor outcome and spatial memory.	Pillay et al., 2007 [72] Hicks et al., 2002 [69]
C5aR antagonist	C5aR	C5a anaphylatoxin	Decreased neutrophil extravasation in the brain.	Sewell et al., 2004 [67]

See text for details and explanations.