Table 1.

Summary of complement effects on the TBI process in animals models and human studies.

Human	Complement analysis	Complement levels	References
Severe TBI	C3/CFB	↑CSF	Kossmann et al., 1997
Severe TBI	C3/C1q/C4	↑CSF	Stahel et al., 1998
Severe TBI	C5b9	↑CSF	Stahel et al., 2001
Severe TBI	C3/C9	↑Plasma	Bao et al., 2018
Severe TBI	MBL	↑Plasma	Osthoff et al., 2017
Animal models	Complement target	Complement biologic effects	References
Cortical impact (severe TBI)	C9/CFB	↑Serum	Thelin et al., 2018
Cortical contusion (severe TBI)	C3	↑Deposits (peri-lesion tissue)	Bellander et al., 1996
Cortical contusion (severe TBI)	C9	↑Deposits (damaged neurons)	Bellander et al., 1996
Intra-cerebral hemorrhage	C3−/− mice	↓Brain edema ↓Microglia activation/infiltration	Sewell et al., 2004; Yang et al., 2006
Severe TBI swine resuscitation	CD59/C1q	↓Complement system activation associated to a decrease of lesion size	Dekker et al., 2014a,b; Bambakidis et al., 2016
Cortical impact (severe TBI)	CD59−/− mice	↑Neuronal cell death	Stahel et al., 2009
Severe closed head injury mice	C6 antisense oligonucleotide Or C5 convertase inhibition	↓C5b9 deposits/axon loss ↓Microglia/macrophage accumulation ↓Neuronal cells death ↑Neurologic perfomances	Fluiter et al., 2014
Cortical impact (severe TBI)	C3 cleavage inhibition	↓Microglial/astrocyte activations ↓C3 deposits/neuron cells death ↑Cognitive/functional recovery	Rich et al., 2016; Alawieh et al., 2018
Focal trauma (severe TBI)	cfb−/− mice	↓Neuronal cell death	Leinhase et al., 2006
Focal trauma (severe TBI)	Anti-CFB antibody	↓Inflammation/cell death	Leinhase et al., 2007
Cortical impact (severe TBI)	C1q inhibitor	↓Cognitive dysfunction/contusion volumes	Longhi et al., 2009
Cortical impact (severe TBI)	MBL	↑MBL deposits (injured cortex)	Longhi et al., 2014
Cortical impact (severe TBI)	mbl−/− mice	↑Cortical cell death	Longhi et al., 2014

CSF, CerebroSpinal Fluid; MBL, Mannose Binding Lectin protein.