Aspirin ameliorates cerebral infarction through regulation of TLR4/NF‑κB‑mediated endoplasmic reticulum stress in mouse model

Wang,Xin; Shen,Bin; Sun,Dezhou; Cui,Xiangyu

doi:10.3892/mmr.2017.7879

Aspirin ameliorates cerebral infarction through regulation of TLR4/NF‑κB‑mediated endoplasmic reticulum stress in mouse model

Authors:
- Xin Wang
- Bin Shen
- Dezhou Sun
- Xiangyu Cui
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Affiliations: Department of Neurosurgery, Dezhou People's Hospital, Dezhou, Shandong 420065, P.R. China
Published online on: October 25, 2017 https://doi.org/10.3892/mmr.2017.7879
Pages: 479-487

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Abstract

Cerebral infarction is a cerebrovascular disease caused by local brain ischemic necrosis or softening, which is associated with diabetes, obesity, hypertension and rheumatic heart arrhythmia. Previous studies have indicated that aspirin is a potential oral anticoagulant in the treatment of cerebral ischemic stroke. However, the potential mechanism mediated by aspirin in cerebral infarction therapy is not well understood. The present study analyzed the therapeutic effects of aspirin on cerebral infarction and investigated the underlying molecular mechanism of aspirin‑ameliorated benefits for thrombolysis. The results demonstrated that aspirin inhibited inflammation and apoptosis of cerebrovascular endothelial cells in a mouse model of cerebral infarction. Aspirin treatment suppressed toll‑like receptor (TLR)4 and nuclear factor (NF)‑κB expression in cerebrovascular endothelial cells. Endoplasmic reticulum (ER) stress was suppressed by aspirin treatment through the downregulation of protein kinase R‑like endoplasmic reticulum kinase, eukaryotic translation initiation factor 2 subunit 1 and C/EBP homologous protein expression levels in cerebrovascular endothelial cells. It was identified that knockdown of TLR4 inhibited aspirin‑mediated downregulation of NF‑κB signaling pathway and ER stress in cerebrovascular endothelial cells. Expression levels of adenosine diphosphate plasminogen activator inhibitors, von Willebrand factor and thromboxane were downregulated in cerebrovascular endothelial cells and in serum in experimental mice. The results demonstrated that aspirin was beneficial forthrombolysis by decreasing thrombin‑activatable fibrinolysis inhibitor and plasminogen activator inhibitor‑1 expression in a mouse model of cerebral infarction. These results suggested that aspirin may improve cerebral infarction by downregulating TLR4/NF‑κB‑mediated ER stress in a mouse model.

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