Department of Neurology, General Hospital of Shenyang Military Region, Shenyang 110840, PR China.
Department of Neurology, General Hospital of Shenyang Military Region, Shenyang 110840, PR China.
Brain Res. 2018 Dec 15;1701:237-245. doi: 10.1016/j.brainres.2018.09.029. Epub 2018 Sep 21.
We propose that the neuroprotective effect of glucocorticoid in ischemic damage may be time dependent. The present study was designed to test the proposal and its possible mechanismin cerebral ischemia/reperfusion (I/R) injury model. Reperfusion injury was induced after 120 min of middle cerebral artery occlusion (MCAO) in male Sprague-Dawley rats. Atdifferenttimepoints after MCAO, rats were treated with high dose dexamethasone (10 mg/kg), and neurological deficit and infarct sizes were measured 2 h, 24 h after MCAO. The expression of NF-κB target genes, including inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were determined by western blot analysis and ELISA. Dexamethasone delivered 30 min (but not 60 min, 120 min) after MCAO markedly decreased the infarct size, improved neurological deficits in I/R injury model. Dexamethasone delivered 30 min (but not 60 min) after MCAO significantly inhibited NF-κB p65 expression and phosphorylation, compared with I/R group. The expression of iNOS, COX-2, TNF-α and IL-1β, were also suppressed by dexamethasone delivered 30 min (but not 60 min) after MCAO. The results imply that neuroprotective action of dexamethasone in focal ischemic stroke model may be time dependent and attributed to inhibiting inflammation-related NF-κB p65 pathways.
我们提出，糖皮质激素对缺血性损伤的神经保护作用可能具有时间依赖性。本研究旨在检验这一假说及其在脑缺血/再灌注（I/R）损伤模型中的可能机制。雄性 Sprague-Dawley 大鼠在大脑中动脉闭塞（MCAO） 120 分钟后诱导再灌注损伤。在 MCAO 后的不同时间点，用高剂量地塞米松（10mg/kg）处理大鼠，并在 MCAO 后 2 小时和 24 小时测量神经功能缺损和梗死面积。通过 Western blot 分析和 ELISA 测定 NF-κB 靶基因，包括诱导型一氧化氮合酶（iNOS）、环氧化酶（COX-2）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的表达。地塞米松在 MCAO 后 30 分钟（而不是 60 分钟、120 分钟）给药可显著降低梗死面积，改善 I/R 损伤模型中的神经功能缺损。与 I/R 组相比，地塞米松在 MCAO 后 30 分钟（而不是 60 分钟）给药可显著抑制 NF-κB p65 表达和磷酸化。iNOS、COX-2、TNF-α 和 IL-1β 的表达也被 MCAO 后 30 分钟（而不是 60 分钟）给予的地塞米松抑制。结果表明，地塞米松在局灶性缺血性中风模型中的神经保护作用可能具有时间依赖性，这归因于抑制与炎症相关的 NF-κB p65 通路。
