Department of Pharmacology, Stony Brook University, Stony Brook, NY 11794-8651, USA.
J Neuroinflammation. 2012 Jul 3;9:159. doi: 10.1186/1742-2094-9-159.
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.
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.
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.
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.
缺血性中风在数小时内会引起梗死核心区的神经元死亡，并在较长时间内引起周围区域的继发性损伤。使用药理试剂减轻炎症已成为中风治疗研究的目标。环氧化酶 2（COX-2）是炎症的标志物，在中风期间被诱导，并通过释放酶产物（如前列腺素（PG）E2）增强炎症反应。
野生型（WT）和 COX-2 敲除（COX-2KO）小鼠接受大脑中动脉闭塞（MCAO）。此外，从这些小鼠或脑微血管内皮细胞（BMEC）中取出脑切片，并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，并与炎症状态相关联。
我们发现，在 MCAO 或 OGD 后，ECM 的成分，特别是层粘连蛋白，在内皮细胞上短暂地高度上调。在 COX-2KO 小鼠或用 COX-2 抑制剂塞来昔布治疗的 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。
综上所述，我们报告称，中风后早期会发生短暂的 ECM 重塑，并表明 ECM 蛋白表达的增加可能是为了重新血管化和为组织供氧。
