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.
|Titolo:||C1-inhibitor protects against brain ischemia-reperfusion injury via inhibition of cell recruitment and inflammation|
BERGAMASCHINI, LUIGI CESARE (Penultimo)
|Parole Chiave:||Apoptosis; C1-inhibitor; Cell infiltration; Inflammation; Middle cerebral artery occlusion; Neurodegeneration|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||2005|
|Digital Object Identifier (DOI):||10.1016/j.nbd.2004.11.001|
|Appare nelle tipologie:||01 - Articolo su periodico|