We investigated the effects of simvastatin treatment on the expression of IL-1beta and MCP-1, the activity of NF-kB, and the signaling pathways related to NF-kB activation in a rat model of permanent middle cerebral artery occlusion (pMCAO). IL-1beta and MCPA expression, determined using RT-PCR, was enhanced by pMCAO; this effect was inhibited by the administration of simvastatin before ischemia. Pre-treatment with simvastatin abolished the ischemia-induced activation of NF-kB observed in vehicle-treated animals. The evaluation of signal transduction pathways, including extracellular signal-regulated kinase (ERK1/2), SAPK/JNK 46/54 and p38, indicated that only ERK1/2 phosphorylation was enhanced by ischemia, and this activation was prevented by simvastatin. ERK1/2-inhibitor, U0126, reduced brain ischemia but not cytokine induction. These results provide evidence that the HMG-CoA reductase inhibitor induces its effect in the protection of ischemic brain damage with a more complex mechanism which also involve anti-inflammatory properties rather than simple inhibition of ERK1/2 signaling pathway. (c) 2005 Elsevier Inc. All rights reserved.
Activation of NF-kB and ERK1/2 after permanent focal ischemia is abolished by simvastatin treatment / L. SIRONI, C. BANFI, M. BRIOSCHI, P. GELOSA, U. GUERRINI, E. NOBILI, A. GIANELLA, R. PAOLETTI, E. TREMOLI, M. CIMINO. - In: NEUROBIOLOGY OF DISEASE. - ISSN 0969-9961. - 22:2(2006), pp. 445-451.
|Titolo:||Activation of NF-kB and ERK1/2 after permanent focal ischemia is abolished by simvastatin treatment|
SIRONI, LUIGI (Primo)
BANFI, CRISTINA (Secondo)
TREMOLI, ELENA (Penultimo)
|Parole Chiave:||statin; inflammation; cerebral ischemia; permanent middle; cerebral artery occlusion; transcription factor; MAP kinase; rat|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2006|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.nbd.2005.12.004|
|Appare nelle tipologie:||01 - Articolo su periodico|