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. (copyright) 2004 Elsevier Inc. All rights reserved.

C1-inhibitor protects against brain ischemia-reperfusion injury via inhibition of cell recruitment and inflammation / C. Storini, E. Rossi, V. Marrella, M. Distaso, R. Veerhuis, C. Vergani, L.C. Bergamaschini, M.-G. De Simoni. - In: NEUROBIOLOGY OF DISEASE. - ISSN 0969-9961. - 19:1-2(2005), pp. 10-17. [10.1016/j.nbd.2004.11.001]

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

C. Vergani;L.C. Bergamaschini
Penultimo
;
2005

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 (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. (copyright) 2004 Elsevier Inc. All rights reserved.
Apoptosis; C1-inhibitor; Cell infiltration; Inflammation; Middle cerebral artery occlusion; Neurodegeneration
Settore MED/09 - Medicina Interna
2005
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/17231
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