Brain edema after intracerebral hemorrhage: the effects of systemic complement depletion.
The complement cascade is activated after experimental intracerebral hemorrhage (ICH) and may play an important, role in edema formation. This study investigated the effects of systemic complement depletion on brain edema formation following ICH. Thirty-six pentobarbital-anesthetized Sprague-Dawley rats were used. Treatment animals were complement-depleted with cobra venom factor (CVF) while controls received an equal volume of saline injection (i.p.). In both treatment and control rats, autologous blood (100-microL) was infused stereotactically into the right basal ganglia. Rats were sacrificed one and three days later for brain water and ion content measurements and immunohistochemical studies. Immunohistochemistry was used to detect complement C3d, C5a, and C9. Western blot analysis was applied for C9 semiquantitation. Perihematomal brain edema was reduced by systemic complement depletion at one and three days. The water content of the cerebellum (a tissue distant from the hematoma site) was unaffected by complement depletion. Immunocytochemistry found complement depletion significantly reduced perihematomal C9 deposition, C3d production, and C5a positive cell accumulation. In conclusion, complement depletion by CVF attenuates brain edema in ICH perhaps by inhibiting the inflammatory response and membrane attack complex (MAC) formation.
Xi
G
G
Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor, Michigan, USA.
Hua
Y
Y
Keep
R F
RF
Younger
J G
JG
Hoff
J T
JT
D000818:Animals; D001929:Brain Edema / Q000097:blood / Q000209:etiology*; D003165:Complement System Proteins / Q000172:deficiency* / Q000187:drug effects; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000494:pharmacology; D020300:Intracranial Hemorrhages / Q000097:blood* / Q000150:complications; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D004546:Elapid Venoms; C016310:cobra venom factor; D003165:Complement System Proteins