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Inflammation modulates expression of laminin in the central nervous system following ischemic injury

机译:炎症调节缺血性损伤后中枢神经系统中层粘连蛋白的表达

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Background Ischemic stroke induces neuronal death in the core of the infarct within a few hours and the secondary damage in the surrounding regions over a long period of time. Reduction of inflammation using pharmacological reagents has become a target of research for the treatment of stroke. Cyclooxygenase 2 (COX-2), a marker of inflammation, is induced during stroke and enhances inflammatory reactions through the release of enzymatic products, such as prostaglandin (PG) E2. Methods Wild-type (WT) and COX-2 knockout (COX-2KO) mice were subjected to middle cerebral artery occlusion (MCAO). Additionally, brain slices derived from these mice or brain microvascular endothelial cells (BMECs) were exposed to oxygen-glucose deprivation (OGD) conditions. The expression levels of extracellular matrix (ECM) proteins were assessed and correlated with the state of inflammation. Results We found that components of the ECM, and specifically laminin, are transiently highly upregulated on endothelial cells after MCAO or OGD. This upregulation is not observed in COX-2KO mice or WT mice treated with COX-2 inhibitor, celecoxib, suggesting that COX-2 is associated with changes in the levels of laminins. Conclusions Taken together, we report that transient ECM remodeling takes place early after stroke and suggest that this increase in ECM protein expression may constitute an effort to revascularize and oxygenate the tissue.
机译:背景技术缺血性中风会在数小时内在梗塞的核心区域引起神经元死亡,并在很长一段时间内在周围区域引起继发性损伤。使用药理学试剂减轻炎症已成为中风治疗研究的目标。环氧乙烷加氧酶2(COX-2)是发炎的一种标志物,在中风时被诱导并通过释放诸如前列腺素(PG)E2之类的酶促产物来增强炎症反应。方法对野生型(WT)和COX-2敲除(COX-2KO)小鼠进行大脑中动脉闭塞(MCAO)。此外,将源自这些小鼠或脑微血管内皮细胞(BMEC)的脑片暴露于氧-葡萄糖剥夺(OGD)条件下。评估细胞外基质(ECM)蛋白的表达水平,并将其与炎症状态相关联。结果我们发现,在MCAO或OGD之后,内皮细胞上的ECM成分,特别是层粘连蛋白,瞬时上调。在用COX-2抑制剂塞来昔布治疗的COX-2KO小鼠或WT小鼠中未观察到这种上调,表明COX-2与层粘连蛋白水平的变化有关。结论综上所述,我们报道了短暂性ECM重塑发生在中风后早期,并表明ECM蛋白表达的这种增加可能构成了使组织血运和充氧的努力。

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