The role of complement C3 in intracerebral hemorrhage-induced brain injury.
Activation of the complement cascade contributes to brain injury after intracerebral hemorrhage (ICH). However, a recent study found that complement C5 deficient mice had enhanced ICH-induced brain injury. The present study, therefore, investigated the role of complement C3 (which is upstream from C5) in ICH. Male complement C3 deficient and sufficient mice had an intracerebral infusion of 30-muL autologous whole blood. The mice were killed and the brains were sampled for edema, Western blotting, immunohistochemistry and histologic analysis. Behavioral tests including forelimb use asymmetry test and corner turn were also performed before and after ICH. Compared to complement C3 sufficient mice, C3 deficient mice had less brain edema, lower hemeoxygenase-1 levels, less microglia activation and neutrophil infiltration around the clot after ICH. In addition, the C3-deficient mice had less ICH-induced forelimb use asymmetry deficits compared with C3-sufficient mice. These results suggest complement activation may affect heme metabolism and the inflammatory response after ICH suggesting that complement C3 is an important factor causing ICH-induced brain injury.
Yang
Shuxu
S
Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109-0532, USA.
Nakamura
Takehiro
T
Hua
Ya
Y
Keep
Richard F
RF
Younger
John G
JG
He
Yangdong
Y
Hoff
Julian T
JT
Xi
Guohua
G
D000818:Animals; D001522:Behavior, Animal; D001929:Brain Edema / Q000201:enzymology / Q000235:genetics; D001930:Brain Injuries / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D003167:Complement Activation / Q000235:genetics; D003176:Complement C3 / Q000172:deficiency / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000201:enzymology / Q000473:pathology
D003176:Complement C3; D051547:Heme Oxygenase-1