Jin Guimin, Han Wei, Duan Tingting, Xue Zongwei, Song Chenglin, Xu Yuhao, Yu Ming
Department of Neurology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, Jiangsu, China.
Nutritional Department, The Second People'S Hospital of Lianyungang, Lianyungang, 222000, China.
Metab Brain Dis. 2025 Mar 3;40(3):134. doi: 10.1007/s11011-025-01559-0.
Edaravone dextrose (EDB) is a commonly used clinical treatment for cerebral infarction due to its anti-inflammatory and free radical scavenging properties. However, its potential additional neuroprotective mechanisms need to be further investigated. In this study, we evaluated the effects of EDB on ferroptosis, cuproptosis, and blood-brain barrier (BBB) disruption after cerebral infarction in vivo and in vitro by constructing a mouse middle cerebral artery occlusion (MCAO) model, and an oxygen-glucose deprivation/reperfusion (OGD/R) model of neurons and brain microvascular endothelium. Our results showed that EDB treatment improved neurological impairment and brain histopathology in MCAO mice. EDB treatment significantly alleviated ferroptosis and cuproptosis in MCAO mice and OGD/R models of neuronal, in vitro and in vivo, the protective pathway of ferroptosis SLC7A11/GPX4 was detected to be activated and the cuproptosis-promoting protein SLC31A1 and FDX1 were down-regulated. We also found that EDB treatment ameliorated BBB damage in MCAO mice. The endothelial cell protective pathway PDGFRβ/PI3K/AKT activation was also detected in MCAO mice and OGD/R models of endothelial cells after EDB treatment. In conclusion, our study demonstrated that EDB has a good ameliorating effect on ferroptosis, cuproptosis, and BBB damage after cerebral infarction, which provides more evidence for the clinical application of EDB and provides new theories and directions for the study of the mechanism of EDB.
依达拉奉右旋糖酐（EDB）因其抗炎和清除自由基的特性，是临床上常用的脑梗死治疗药物。然而，其潜在的额外神经保护机制尚需进一步研究。在本研究中，我们通过构建小鼠大脑中动脉闭塞（MCAO）模型以及神经元和脑微血管内皮细胞的氧糖剥夺/再灌注（OGD/R）模型，在体内和体外评估了EDB对脑梗死铁死亡、铜死亡和血脑屏障（BBB）破坏的影响。我们的结果表明，EDB治疗改善了MCAO小鼠的神经功能缺损和脑组织病理学。EDB治疗显著减轻了MCAO小鼠以及体外和体内神经元OGD/R模型中的铁死亡和铜死亡，检测到铁死亡的保护途径SLC7A11/GPX4被激活，促铜死亡蛋白SLC31A1和FDX1下调。我们还发现，EDB治疗改善了MCAO小鼠的血脑屏障损伤。在EDB治疗后的MCAO小鼠和内皮细胞OGD/R模型中，也检测到内皮细胞保护途径PDGFRβ/PI3K/AKT的激活。总之，我们的研究表明，EDB对脑梗死后的铁死亡、铜死亡和血脑屏障损伤具有良好的改善作用，这为EDB的临床应用提供了更多证据，并为EDB作用机制的研究提供了新的理论和方向。
