Cerebral ischemia is the most common cause of hippocampal neuronal death and the most prevalent cause of stroke with high mortality rate. Ferroptosis has been suggested to affect the role of hippocampal neurons. This study explores the influence of lentivirus infection-induced ferritin overexpression in hippocampal neuronal injury and death through simulations in August Copenhagen Irish rat models. Twenty-four-hour cerebral ischemia–reperfusion injury was induced in the rats after 90-min middle cerebral artery occlusion (MCAO). Ferritin overexpression was induced through lentivirus infection. The Morris Water Maze (MWM) test and tau hyperphosphorylation test were performed on hippocampal neurons to establish a MCAO model. The effect of ferritin overexpression on hippocampal neuronal death was evaluated using hematoxylin–eosin staining and annexin V/propidium iodide flow cytometry. The MWM test revealed that MCAO modeling decreased the cognitive and locomotor capacity of the rats, whereas ferritin overexpression partially reversed the effect of MCAO. In addition, the hyperphosphorylation of tau caused by MCAO was reduced by ferritin. Pathogenic changes, impaired viability, increased apoptosis, and elevated caspase-9 cleavage in hippocampal neurons were clearly recovered by ferritin. Moreover, robust reactive oxygen species production and glutathione consumption, which was induced by MCAO modeling, were ameliorated by ferritin. Furthermore, two key modulators of ferroptosis, p53 and SLC7A11, were demonstrated to be upregulated by MCAO modeling and downregulated by ferritin. Ferritin reduction is essential for cerebral ischemia-induced hippocampal neuronal ferroptosis mediated via p53 and SLC7A11.

脑缺血是海马神经元死亡的最常见原因，也是死亡率高的中风的最常见原因。已经提出铁死亡会影响海马神经元的作用。本研究通过八月哥本哈根爱尔兰大鼠模型中的模拟，探讨了慢病毒感染诱导的铁蛋白过表达对海马神经元损伤和死亡的影响。大脑中动脉闭塞 (MCAO) 90 分钟后，大鼠出现 24 小时脑缺血再灌注损伤。通过慢病毒感染诱导铁蛋白过表达。对海马神经元进行Morris水迷宫（MWM）试验和tau过度磷酸化试验，建立MCAO模型。使用苏木精-伊红染色和膜联蛋白 V/碘化丙啶流式细胞术评估铁蛋白过表达对海马神经元死亡的影响。MWM 测试显示，MCAO 模型降低了大鼠的认知和运动能力，而铁蛋白过表达部分逆转了 MCAO 的作用。此外，由 MCAO 引起的 tau 过度磷酸化被铁蛋白降低。铁蛋白清楚地恢复了海马神经元中的致病性变化、活力受损、细胞凋亡增加和 caspase-9 切割升高。此外，由 MCAO 模型诱导的强劲的活性氧产生和谷胱甘肽消耗被铁蛋白改善。此外，铁死亡的两个关键调节剂 p53 和 SLC7A11，被证明被MCAO模型上调并被铁蛋白下调。铁蛋白减少对于通过 p53 和 SLC7A11 介导的脑缺血诱导的海马神经元铁死亡至关重要。