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(Stroke. 2001;32:162.)
© 2001 American Heart Association, Inc.

Original Contributions

Systemic Complement Depletion Diminishes Perihematomal Brain Edema in Rats

Guohua Xi, MD; Ya Hua, MD; Richard F. Keep, PhD; John G. Younger, MD Julian T. Hoff, MD

From the Departments of Surgery (Neurosurgery) (G.X., Y.H., R.F.K., J.T.H.), Physiology (R.F.K.), and Emergency Medicine (J.G.Y.), University of Michigan, Ann Arbor.

Background and Purpose—The complement cascade is activated after experimental intracerebral hemorrhage (ICH). It remains unclear, however, whether depleting the complement system will improve injury resulting from ICH. This study investigated the effects of systemic complement depletion on brain edema formation after ICH.

Methods—Fifty-six pentobarbital-anesthetized Sprague-Dawley rats were used. Treatment animals were complement-depleted with cobra venom factor (CVF) (intraperitoneally). Control rats received an equal volume of saline injection (intraperitoneally). In both treatment and control rats, autologous blood (100 µL) was infused stereotaxically into the right basal ganglia. Rats were killed 2, 24, or 72 hours later for brain water, ion, and tumor necrosis factor- (TNF-) measurements, for Western blot analysis, and for immunohistochemical studies. Brain edema was quantitated by wet/dry weight. TNF- levels were measured by enzyme-linked immunosorbent assay. Western blot analysis was applied for C9 semiquantification. Immunohistochemistry was used to detect complement C3d, C5a, C9, and myeloperoxidase.

Results—Perihematomal brain edema was reduced by systemic complement depletion at 24 hours (78.8±0.6% versus 81.5±0.8% in control, P<0.01) and 72 hours (81.5±1.5% versus 83.6±0.9% in control, P<0.05), while cerebellar water content was unaffected (78.2±0.3% versus 78.0±0.1%). Complement depletion reduced TNF- production 2 hours after ICH. Immunocytochemistry showed that complement depletion significantly reduced perihematomal C9 deposition, C3d production, and the number of C5a- and myeloperoxidase-positive cells.

Conclusions—Complement depletion by CVF attenuates brain edema in ICH, indicating that complement activation plays an important role in ICH-induced brain edema. Preventing complement activation may be effective in the treatment of ICH.

Key Words: brain edema • cerebral hemorrhage • complement • tumor necrosis factor • rats

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