Simvastatin Reduces Lipopolysaccharides-Accelerated Cerebral Ischemic Injury via Inhibition of Nuclear Factor-kappa B Activity
- Authors
- Jalin, Angela M. A. Anthony; Lee, Jae-Chul; Cho, Geum-Sil; Kim, Chunsook; Ju, Chung; Pahk, Kisoo; Song, Hwa Young; Kim, Won-Ki
- Issue Date
- 1-11월-2015
- Publisher
- KOREAN SOC APPLIED PHARMACOLOGY
- Keywords
- Simvastatin; Cerebral Stroke; Cytokine; Inflammation; Macrophages; Microglia
- Citation
- BIOMOLECULES & THERAPEUTICS, v.23, no.6, pp.531 - 538
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- BIOMOLECULES & THERAPEUTICS
- Volume
- 23
- Number
- 6
- Start Page
- 531
- End Page
- 538
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/91957
- DOI
- 10.4062/biomolther.2015.124
- ISSN
- 1976-9148
- Abstract
- 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.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.