Pharmacological inhibition of TLR4-NOX4 signal protects against neuronal death in transient focal ischemia
説明
Recent data have shown that TLR4 performs a key role in cerebral ischemia-reperfusion injury which serves as the origin of the immunological inflammatory reactions. However, the therapeutic effects of pharmacological inhibitions of TLR4 and its immediate down-stream pathway remain to be uncovered. In the present study, on mice, intracerebroventricular injection of resatorvid (TLR4 signal inhibitor; 0.01 μg) significantly reduced infarct volume and improved neurological score after middle cerebral artery occlusion and reperfusion. The levels of phospho-p38, nuclear factor-kappa B, and matrix metalloproteinase 9 expressions were significantly suppressed in the resatorvid-treated group. In addition, NOX4 associates with TLR4 after cerebral ischemia-reperfusion seen in mice and human. Genetic and pharmacological inhibitions of TLR4 each reduced NOX4 expression, leading to suppression of oxidative/nitrative stress and of neuronal apoptosis. These data suggest that resatorvid has potential as a therapeutic agent for stroke since it inhibits TLR4-NOX4 signaling which may be the predominant causal pathway.
収録刊行物
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- Scientific Reports
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Scientific Reports 2 (1), 896-, 2012-11-28
Springer Science and Business Media LLC
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キーワード
- Male
- Apoptosis
- Mice, Inbred Strains
- Article
- Brain Ischemia
- Mice
- Young Adult
- Animals
- Humans
- Neurons
- Sulfonamides
- Cell Death
- NF-kappa B
- NADPH Oxidases
- Infarction, Middle Cerebral Artery
- Middle Aged
- Toll-Like Receptor 4
- Disease Models, Animal
- Oxidative Stress
- Matrix Metalloproteinase 9
- NADPH Oxidase 4
- Case-Control Studies
- Reperfusion Injury
- Female
- Reactive Oxygen Species
- Signal Transduction
詳細情報 詳細情報について
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- CRID
- 1360004233524772224
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- ISSN
- 20452322
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- PubMed
- 23193438
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE
