The hippocampal cell death that follows kainic acid (KA)-induced seizures is associated with blood–brain barrier (BBB) leakage and oxidative stress. Lipocalin-2 (LCN2) is an iron-trafficking protein which contributes to both oxidative stress and inflammation. However, LCN2’s role in KA-induced hippocampal cell death is not clear. Here, we examine the effect of blocking LCN2 genetically on neuroinflammation and oxidative stress in KA-induced neuronal death. LCN2 deficiency reduced neuronal cell death and BBB leakage in the KA-treated hippocampus. In addition to LCN2 upregulation in the KA-treated hippocampus, circulating LCN2 levels were significantly increased in KA-treated wild-type (WT) mice. In LCN2 knockout mice, we found that the expressions of neutrophil markers myeloperoxidase and neutrophil elastase were decreased compared to their expressions in WT mice following KA treatment. Furthermore, LCN2 deficiency also attenuated KA-induced iron overload and oxidative stress in the hippocampus. These findings indicate that LCN2 may play an important role in iron-related oxidative stress and neuroinflammation in KA-induced hippocampal cell death.

中文翻译：

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Lipocalin-2缺乏症可减少氧化应激和神经炎症，并减轻海因酸诱导的海马细胞死亡

海藻酸（KA）诱发的癫痫发作后海马细胞死亡与血脑屏障（BBB）泄漏和氧化应激有关。Lipocalin-2（LCN2）是一种铁转运蛋白，可导致氧化应激和炎症。但是，LCN2在KA诱导的海马细胞死亡中的作用尚不清楚。在这里，我们检查了遗传上阻断LCN2对KA诱导的神经元死亡中神经炎症和氧化应激的影响。LCN2缺乏症减少了KA治疗的海马中神经元细胞死亡和BBB渗漏。除了在KA处理的海马中LCN2上调外，在KA处理的野生型（WT）小鼠中循环LCN2水平也显着增加。在LCN2基因敲除小鼠中，我们发现，KA处理后，中性粒细胞标志物髓过氧化物酶和中性粒细胞弹性蛋白酶的表达与野生型小鼠相比降低。此外，LCN2缺乏也减轻了KA诱导的海马铁超载和氧化应激。这些发现表明，LCN2可能在KA诱导的海马细胞死亡中在铁相关的氧化应激和神经炎症中起重要作用。