Amifostine is a cytoprotective compound that is beneficial in ischaemic stroke cases. However, the neuroprotective effect of amifostine on ischaemia/reperfusion (I/R)-induced brain injury and its underlying mechanism are still poorly understood. Herein, we constructed an animal model of middle cerebral artery occlusion and reperfusion (MCAO/R) injury and an in vitro model of oxygen and glucose deprivation and reperfusion (OGD/R) injury. After administration of amifostine, we found significant improvements in neurological deficits, infarct size, and cerebral oedema. Moreover, amifostine alleviated histopathological alteration and increased the number of surviving neurons. Biochemical analysis showed that treatment with amifostine obviously improved the brain damage of MCAO/R mice, as manifested by a decrease in reactive oxygen species (ROS) and malondialdehyde (MDA) generation, and an increase in superoxide dismutase (SOD) activity. Moreover, amifostine decreased the mitochondrial membrane potential (m) loss, and cytochrome c escaping to cytoplasm, but increased the ATP level. In vitro, amifostine also showed an antioxidant effect, which was reflected by the reduced ROS generation, decreased mitochondrial superoxide generation, increased total SOD, SOD1 (Cu/Zn SOD, cytoplasmic SOD), and SOD2 (mitochondrial SOD) activities, and decreased m loss. Furthermore, amifostine suppressed neuronal apoptosis, accompanied by the reduction of Bax, cleaved caspase-9, cleaved caspase-3, and Bcl-2 upregulation. Amifostine also reduced the expression of p-p38 (Thr 180/Tyr 182) in vivo and in vitro. In short, amifostine exhibits a protective effect on cerebral I/R damage through modulating p38-related oxidative stress, mitochondrial dysfunction, and apoptosis.

中文翻译：

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氨磷汀通过 p38 介导的氧化应激和线粒体功能障碍改善脑缺血再灌注损伤

Amifostine 是一种细胞保护化合物，对缺血性中风病例有益。然而，氨磷汀对缺血/再灌注（I/R）诱导的脑损伤的神经保护作用及其潜在机制仍知之甚少。在此，我们构建了大脑中动脉闭塞再灌注（MCAO/R）损伤的动物模型和氧糖剥夺再灌注（OGD/R）损伤的体外模型。给予氨磷汀后，我们发现神经功能缺损、梗塞面积和脑水肿有显着改善。此外，氨磷汀减轻了组织病理学改变并增加了存活神经元的数量。生化分析表明氨磷汀治疗明显改善了MCAO/R小鼠的脑损伤，表现为活性氧 (ROS) 和丙二醛 (MDA) 生成减少，以及超氧化物歧化酶 (SOD) 活性增加。此外，氨磷汀减少线粒体膜电位（m）损失，细胞色素c逃逸到细胞质，但增加ATP水平。在体外，氨磷汀还表现出抗氧化作用，表现为减少 ROS 生成，减少线粒体超氧化物生成，增加总 SOD、SOD1（Cu/Zn SOD，细胞质 SOD）和 SOD2（线粒体 SOD）活性，并降低  m 损失。此外，氨磷汀抑制神经元凋亡，伴随着 Bax、cleaved caspase-9、cleaved caspase-3 和 Bcl-2 上调的减少。Amifostine 还在体内和体外降低 p-p38 (Thr 180/Tyr 182) 的表达。简而言之，