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. | |
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] |