The Powerful Neuroprotective Action of C1-Inhibitor on Brain Ischemia-Reperfusion Injury Does Not Require C1q

Maria Grazia De Simoni, Emanuela Rossi, Claudio Storini, Simone Pizzimenti, Cinara Echart, Luigi Bergamaschini

Research output: Contribution to journalArticlepeer-review

Abstract

C1-inhibitor (C1-INH) is a major regulator of the complement classical pathway. Besides this action, it may also inhibit other related inflammatory systems. We have studied the effect of C1-INH in C57BL/6 mice with focal transient brain ischemia induced by 30 minutes of occlusion of the middle cerebral artery. C1-INH induced a dose-dependent reduction of ischemic volume that, with the dose of 15 U/mouse, reached 10.8% of the volume of saline-treated mice. Four days after ischemia the treated mice had significantly lower general and focal neurological deficit scores. Fluoro-Jade staining, a marker for neuronal degeneration, showed that C1-INH-treated mice had a lower number of degenerating cells. Leukocyte infiltration, as assessed by CD45 immunostaining, was also markedly decreased. We then investigated the response to ischemia in C1q-/- mice. There was a slight, nonsignificant decrease in infarct volume in C1q-/- mice (reduction to 72.3%) compared to wild types. Administration of C1-INH to these mice was still able to reduce the ischemic volume to 31.4%. The study shows that C1-INH has a strong neuroprotective effect on brain ischemia/reperfusion injury and that its action is independent from C1q-mediated activation of classical pathway.

Original languageEnglish
Pages (from-to)1857-1863
Number of pages7
JournalAmerican Journal of Pathology
Volume164
Issue number5
Publication statusPublished - May 2004

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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