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Table 1 Insights from experimental complement inhibition based on genetically engineered mice and pharmacological approaches in models of traumatic brain injury (TBI).

From: Molecular mechanisms of inflammation and tissue injury after major trauma-is complement the "bad guy"?

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]
  1. See text for details and explanations.