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首页> 美国卫生研究院文献>International Journal of Molecular Sciences >Treatment of Neonatal Hypoxic-Ischemic Encephalopathy with Erythropoietin Alone and Erythropoietin Combined with Hypothermia: History Current Status and Future Research
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Treatment of Neonatal Hypoxic-Ischemic Encephalopathy with Erythropoietin Alone and Erythropoietin Combined with Hypothermia: History Current Status and Future Research

机译：单独使用促红细胞生成素和促红细胞生成素联合低温治疗新生儿缺氧缺血性脑病的历史现状和未来研究

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Perinatal hypoxic-ischemic encephalopathy (HIE) remains a major cause of morbidity and mortality. Moderate hypothermia (33.5 °C) is currently the sole established standard treatment. However, there are a large number of infants for whom this therapy is ineffective. This inspired global research to find neuroprotectants to potentiate the effect of moderate hypothermia. Here we examine erythropoietin (EPO) as a prominent candidate. Neonatal animal studies show that immediate, as well as delayed, treatment with EPO post-injury, can be neuroprotective and/or neurorestorative. The observed improvements of EPO therapy were generally not to the level of control uninjured animals, however. This suggested that combining EPO treatment with an adjunct therapeutic strategy should be researched. Treatment with EPO plus hypothermia led to less cerebral palsy in a non-human primate model of perinatal asphyxia, leading to clinical trials. A recent Phase II clinical trial on neonatal infants with HIE reported better 12-month motor outcomes for treatment with EPO plus hypothermia compared to hypothermia alone. Hence, the effectiveness of combined treatment with moderate hypothermia and EPO for neonatal HIE currently looks promising. The outcomes of two current clinical trials on neurological outcomes at 18–24 months-of-age, and at older ages, are now required. Further research on the optimal dose, onset, and duration of treatment with EPO, and critical consideration of the effect of injury severity and of gender, are also required.
机译：围产期缺氧缺血性脑病（HIE）仍然是发病率和死亡率的主要原因。目前，中度低温（33.5°C）是唯一建立的标准治疗方法。但是，有许多婴儿对此疗法无效。这激发了全球性的研究，以寻找增强中度低温的神经保护剂。在这里，我们检查促红细胞生成素（EPO）作为杰出的候选人。新生动物研究表明，EPO损伤后的即刻治疗和延迟治疗可能具有神经保护作用和/或神经修复作用。但是，观察到的EPO治疗的改善通常未达到未受伤动物的对照水平。这表明应该研究EPO治疗与辅助治疗策略的结合。在围产期窒息的非人灵长类动物模型中，EPO加低温治疗可减少脑瘫，从而进行临床试验。最近一项针对HIE新生儿的II期临床试验报告说，与单独的低温治疗相比，EPO加低温治疗的12个月运动结局更好。因此，目前将中度低温和EPO联合治疗新生儿HIE的效果看好。现在需要两项有关18-24个月龄及更高年龄的神经系统结果的临床试验的结果。还需要进一步研究以EPO进行治疗的最佳剂量，开始时间和持续时间，以及对伤害严重程度和性别影响的严格考虑。

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