Department of Neurology, National Taiwan University Hospital, No. 7, Zhongshan S. Rd., Zhongzheng Dist, Taipei, 100225, Taiwan.
Department of Medical Imaging, National Taiwan University Hospital, No. 7, Zhongshan S. Rd., Zhongzheng Dist, Taipei, 100225, Taiwan.
Mol Neurobiol. 2023 Oct;60(10):5902-5914. doi: 10.1007/s12035-023-03448-y. Epub 2023 Jun 26.
Ferroptosis, an iron-dependent form of cell death, is characterized by intracellular accumulation of iron and reactive oxygen species-induced lipid peroxidation. Animal experiments have shown the important roles of ferroptosis in ischemic stroke, but the evidence in human stroke is insufficient. This prospective study evaluated the associations between plasma ferroptosis biomarkers at hyperacute stage and long-term outcomes in patients with acute ischemic stroke undergoing endovascular thrombectomy (EVT). The plasma samples were collected immediately before and after EVT (T1 and T2) and at 24 h (T3) for the 126 stroke patients and once for the 50 stroke-free control subjects. Compared with controls, stroke patients had higher 4-hydroxynonenal (4-HNE) levels at T1 and T2 while lower homocysteine and soluble transferrin receptor (sTfR) levels at T3. In stroke patients, higher National Institutes of Health Stroke Scale scores at admission were correlated with higher 4-HNE and lower sTfR levels. Lower Alberta Stroke Program Early CT (ASPECT) scores and larger infarct core volumes on CT perfusion before EVT were correlated with higher 4-HNE and homocysteine levels. After adjusting for significant parameters, homocysteine levels at T2 were significantly associated with poor functional outcome and mortality at 3 months. In the receiver operating characteristic (ROC) models, adding homocysteine levels at T2 and hemoglobin levels to the reference model for predicting poor functional outcome significantly increased the area under the ROC curve. In summary, this study provides evidence that ferroptosis is associated with stroke severity and outcomes in patients with acute ischemic stroke undergoing EVT.
铁死亡是一种依赖铁的细胞死亡形式，其特征是细胞内铁积累和活性氧诱导的脂质过氧化。动物实验表明铁死亡在缺血性中风中起重要作用，但在人类中风中的证据不足。本前瞻性研究评估了超急性期行血管内血栓切除术（EVT）的急性缺血性中风患者的血浆铁死亡生物标志物与长期结局之间的关系。对 126 例中风患者在 EVT 前（T1 和 T2）和后 24 小时（T3）以及 50 例无中风对照组采集血浆样本。与对照组相比，中风患者在 T1 和 T2 时 4-羟基壬烯醛（4-HNE）水平较高，而 T3 时同型半胱氨酸和可溶性转铁蛋白受体（sTfR）水平较低。在中风患者中，入院时较高的国立卫生研究院中风量表（NIHSS）评分与较高的 4-HNE 和较低的 sTfR 水平相关。EVT 前 CT 灌注的较低美国国立卫生研究院中风量表早期 CT（ASPECT）评分和较大的梗死核心体积与较高的 4-HNE 和同型半胱氨酸水平相关。在调整了显著参数后，T2 时的同型半胱氨酸水平与 3 个月时的不良功能结局和死亡率显著相关。在接受者操作特征（ROC）模型中，将 T2 时的同型半胱氨酸水平和血红蛋白水平添加到预测不良功能结局的参考模型中，显著增加了 ROC 曲线下面积。总之，这项研究提供了证据表明，铁死亡与接受 EVT 的急性缺血性中风患者的中风严重程度和结局相关。
