C1-inhibitor protects against brain ischemia-reperfusion injury via inhibition of cell recruitment and inflammation

Neurobiol Dis. 2005 Jun-Jul;19(1-2):10-7. doi: 10.1016/j.nbd.2004.11.001.


Previous studies demonstrated that C1-inhibitor (C1-INH), a complement and contact-kinin systems inhibitor, is neuroprotective in cerebral ischemia. To investigate the mechanism of this action, we evaluated the expression of neurodegeneration and inflammation-related factors in mice subjected to 2-h ischemia and 2 or 46 h reperfusion. C1-INH significantly dampened the mRNA expression of the adhesion molecules P-selectin and ICAM-1 induced by the ischemic insult. It significantly decreased the pro-inflammatory cytokine (TNF alpha, IL-18) and increased the protective cytokine (IL-6, IL-10) gene expression. C1-INH treatment prevented the decrease of NFH gene, a marker of cellular integrity and counteracted the increase of pro-caspase 3, an apoptosis index. Furthermore, C1-INH markedly inhibited the activation and/or recruitment of microglia/macrophage, as shown by immunohistochemistry. In conclusion, C1-INH exerts an anti-inflammatory and anti-apoptotic action on ischemia-reperfusion injury. Our present and past data support a major effect of C1-INH on cell recruitment from the vasculature to the ischemic site.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / immunology
  • Brain Ischemia / pathology
  • Brain Ischemia / prevention & control*
  • Cell Adhesion Molecules / antagonists & inhibitors
  • Cell Adhesion Molecules / biosynthesis
  • Cell Migration Inhibition*
  • Complement C1 Inactivator Proteins / physiology
  • Complement C1 Inactivator Proteins / therapeutic use*
  • Complement C1 Inhibitor Protein
  • Cytokines / antagonists & inhibitors
  • Cytokines / immunology
  • Inflammation Mediators / physiology*
  • Inflammation Mediators / therapeutic use
  • Male
  • Mice
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Reperfusion Injury / immunology
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*


  • Cell Adhesion Molecules
  • Complement C1 Inactivator Proteins
  • Complement C1 Inhibitor Protein
  • Cytokines
  • Inflammation Mediators
  • Neuroprotective Agents