Simvastatin reduces lipopolysaccharides-accelerated cerebral ischemic injury via inhibition of nuclear factor-kappa B activity

Angela M A Anthony Jalin, Jae Chul Lee, Geum Sil Cho, Chunsook Kim, Chung Ju, Kisoo Pahk, Hwa Young Song, Won-Ki Kim

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 languageEnglish
Pages (from-to)531-538
Number of pages8
JournalBiomolecules and Therapeutics
Volume23
Issue number6
DOIs
Publication statusPublished - 2015 Nov 1

Fingerprint

Simvastatin
NF-kappa B
Lipopolysaccharides
Wounds and Injuries
Rats
Brain
Ischemia
Bacterial Meningitides
Chemokine CCL2
Corpus Callosum
Microinjections
Coenzyme A
Brain Ischemia
Interleukin-1
Vascular Diseases
Infiltration
Reperfusion
Assays
Oxidoreductases
Stroke

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 journalArticle

Jalin, Angela M A Anthony ; Lee, Jae Chul ; Cho, Geum Sil ; Kim, Chunsook ; Ju, Chung ; Pahk, Kisoo ; Song, Hwa Young ; Kim, Won-Ki. / Simvastatin reduces lipopolysaccharides-accelerated cerebral ischemic injury via inhibition of nuclear factor-kappa B activity. In: Biomolecules and Therapeutics. 2015 ; Vol. 23, No. 6. pp. 531-538.
@article{6a1f4b72aac14384b4a1dd67e4e18ff4,
title = "Simvastatin reduces lipopolysaccharides-accelerated cerebral ischemic injury via inhibition of nuclear factor-kappa B activity",
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.",
keywords = "Cerebral stroke, Cytokine, Inflammation, Macrophages, Microglia, Simvastatin",
author = "Jalin, {Angela M A Anthony} and Lee, {Jae Chul} and Cho, {Geum Sil} and Chunsook Kim and Chung Ju and Kisoo Pahk and Song, {Hwa Young} and Won-Ki Kim",
year = "2015",
month = "11",
day = "1",
doi = "10.4062/biomolther.2015.124",
language = "English",
volume = "23",
pages = "531--538",
journal = "Biomolecules and Therapeutics",
issn = "1976-9148",
publisher = "Korean Society of Applied Pharmacology",
number = "6",

}

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 -