Complement component C3 mediates inflammatory injury following focal cerebral ischemia

J. Mocco, William J. Mack, Andrew F. Ducruet, Sergei A. Sosunov, Michael E. Sughrue, Benjamin G. Hassid, M. Nathan Nair, Ilya Laufer, Ricardo J. Komotar, M. Claire H. Holland, David J. Pinsky, E. Sander Connolly

Research output: Contribution to journalArticle

141 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)209-217
Number of pages9
JournalCirculation research
Volume99
Issue number2
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

Keywords

  • C3
  • Complement
  • Neuroprotection

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Mocco, J., Mack, W. J., Ducruet, A. F., Sosunov, S. A., Sughrue, M. E., Hassid, B. G., Nair, M. N., Laufer, I., Komotar, R. J., Holland, M. C. H., Pinsky, D. J., & Connolly, E. S. (2006). Complement component C3 mediates inflammatory injury following focal cerebral ischemia. Circulation research, 99(2), 209-217. https://doi.org/10.1161/01.RES.0000232544.90675.42