Complement component C3 mediates inflammatory injury following focal cerebral ischemia

Document Type

Article

Abstract

The complement cascade has been implicated in ischemia/reperfusion injury, and recent studies have shown that complement inhibition is a promising treatment option for acute stroke. The development of clinically useful therapies has been hindered, however, by insufficient understanding of which complement subcomponents contribute to post-ischemic injury. To address this issue, we subjected mice deficient in selected complement proteins (C1q, C3, C5) to transient focal cerebral ischemia. Of the strains investigated, only C3-/- mice were protected, as demonstrated by 34% reductions in both infarct volume (P<0.01) and neurological deficit score (P<0.05). C3-deficient mice also manifested decreased granulocyte infiltration (P<0.02) and reduced oxidative stress (P<0.05). Finally, administration of a C3a-receptor antagonist resulted in commensurate neurological improvement and stroke volume reduction (P<0.05). Together, these results establish C3 activation as the key constituent in complement-related inflammatory tissue injury following stroke and suggest a C3a anaphylatoxin-mediated mechanism.

Medical Subject Headings

Animals; Brain Ischemia (etiology, pathology, prevention & control); Cell Movement; Complement C3 (physiology); Disease Models, Animal; Granulocytes; Inflammation (etiology, pathology, prevention & control); Membrane Proteins (antagonists & inhibitors); Mice; Mice, Knockout; Oxidative Stress; Receptors, Complement (antagonists & inhibitors); Stroke (drug therapy, pathology)

Publication Date

7-21-2006

Publication Title

Circulation research

E-ISSN

1524-4571

Volume

99

Issue

2

First Page

209

Last Page

17

PubMed ID

16778128

Digital Object Identifier (DOI)

10.1161/01.RES.0000232544.90675.42

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