Activation of NF-kB and ERK1/2 after permanent focal ischemia is abolished by simvastatin treatment

Luigi Sironi, Cristina Banfi, Maura Brioschi, Paolo Gelosa, Uliano Guerrini, Elena Nobili, Anita Gianella, Rodolfo Paoletti, Elena Tremoli, Mauro Cimino

Research output: Contribution to journalArticle

Abstract

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 MCP-1 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.

Original languageEnglish
Pages (from-to)445-451
Number of pages7
JournalNeurobiology of Disease
Volume22
Issue number2
DOIs
Publication statusPublished - May 2006

Keywords

  • Cerebral ischemia
  • Inflammation
  • MAP kinase
  • Permanent middle cerebral artery occlusion
  • Rat
  • Statin
  • Transcription factor

ASJC Scopus subject areas

  • Neurology

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