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-1β 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-κB, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of IκB. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.
| Original language | English |
|---|---|
| Pages (from-to) | 531-538 |
| Number of pages | 8 |
| Journal | Biomolecules and Therapeutics |
| Volume | 23 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2015 Nov 1 |
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Keywords
- Cerebral stroke
- Cytokine
- Inflammation
- Macrophages
- Microglia
- Simvastatin
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Drug Discovery
- Pharmacology
Cite this
Simvastatin reduces lipopolysaccharides-accelerated cerebral ischemic injury via inhibition of nuclear factor-kappa B activity. / Jalin, Angela M A Anthony; Lee, Jae Chul; Cho, Geum Sil; Kim, Chunsook; Ju, Chung; Pahk, Kisoo; Song, Hwa Young; Kim, Won-Ki.
In: Biomolecules and Therapeutics, Vol. 23, No. 6, 01.11.2015, p. 531-538.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Simvastatin reduces lipopolysaccharides-accelerated cerebral ischemic injury via inhibition of nuclear factor-kappa B activity
AU - Jalin, Angela M A Anthony
AU - Lee, Jae Chul
AU - Cho, Geum Sil
AU - Kim, Chunsook
AU - Ju, Chung
AU - Pahk, Kisoo
AU - Song, Hwa Young
AU - Kim, Won-Ki
PY - 2015/11/1
Y1 - 2015/11/1
N2 - 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-1β 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-κB, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of IκB. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.
AB - 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-1β 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-κB, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of IκB. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.
KW - Cerebral stroke
KW - Cytokine
KW - Inflammation
KW - Macrophages
KW - Microglia
KW - Simvastatin
UR - http://www.scopus.com/inward/record.url?scp=84944734810&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84944734810&partnerID=8YFLogxK
U2 - 10.4062/biomolther.2015.124
DO - 10.4062/biomolther.2015.124
M3 - Article
VL - 23
SP - 531
EP - 538
JO - Biomolecules and Therapeutics
JF - Biomolecules and Therapeutics
SN - 1976-9148
IS - 6
ER -