DOI QR코드

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Simvastatin Reduces Lipopolysaccharides-Accelerated Cerebral Ischemic Injury via Inhibition of Nuclear Factor-kappa B Activity

  • Jalin, Angela M.A. Anthony (Department of Neuroscience, Korea University College of Medicine) ;
  • Lee, Jae-Chul (Department of Neurobiology, School of Medicine, Kangwon National University) ;
  • Cho, Geum-Sil (Department of Neuroscience, Korea University College of Medicine) ;
  • Kim, Chunsook (Department of Nursing, Kyungdong University) ;
  • Ju, Chung (Department of Neuroscience, Korea University College of Medicine) ;
  • Pahk, Kisoo (Department of Neuroscience, Korea University College of Medicine) ;
  • Song, Hwa Young (Department of Neuroscience, Korea University College of Medicine) ;
  • Kim, Won-Ki (Department of Neuroscience, Korea University College of Medicine)
  • 투고 : 2015.08.10
  • 심사 : 2015.08.31
  • 발행 : 2015.11.01

초록

Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusionevoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-$1{\beta}$ in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-${\kappa}B$, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of $I{\kappa}B$. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.

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참고문헌

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