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

Claudio Storini, Emanuela Rossi, Veronica Marrella, Maria Distaso, Robert Veerhuis, Carlo Vergani, Luigi Bergamaschini, Maria Grazia De Simoni

Research output: Contribution to journalArticle

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Abstract

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 (TNFα, 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.

Original languageEnglish
Pages (from-to)10-17
Number of pages8
JournalNeurobiology of Disease
Volume19
Issue number1-2
DOIs
Publication statusPublished - Jun 2005

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Reperfusion Injury
Brain Ischemia
Cytokines
Inflammation
Kinins
Interleukin-18
P-Selectin
Microglia
Intercellular Adhesion Molecule-1
Caspase 3
Interleukin-10
Reperfusion
Interleukin-6
Anti-Inflammatory Agents
Ischemia
Immunohistochemistry
Macrophages
Apoptosis
Gene Expression
Messenger RNA

Keywords

  • Apoptosis
  • C1-inhibitor
  • Cell infiltration
  • Inflammation
  • Middle cerebral artery occlusion
  • Neurodegeneration

ASJC Scopus subject areas

  • Neurology

Cite this

C1-inhibitor protects against brain ischemia-reperfusion injury via inhibition of cell recruitment and inflammation. / Storini, Claudio; Rossi, Emanuela; Marrella, Veronica; Distaso, Maria; Veerhuis, Robert; Vergani, Carlo; Bergamaschini, Luigi; De Simoni, Maria Grazia.

In: Neurobiology of Disease, Vol. 19, No. 1-2, 06.2005, p. 10-17.

Research output: Contribution to journalArticle

Storini, Claudio ; Rossi, Emanuela ; Marrella, Veronica ; Distaso, Maria ; Veerhuis, Robert ; Vergani, Carlo ; Bergamaschini, Luigi ; De Simoni, Maria Grazia. / C1-inhibitor protects against brain ischemia-reperfusion injury via inhibition of cell recruitment and inflammation. In: Neurobiology of Disease. 2005 ; Vol. 19, No. 1-2. pp. 10-17.
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