Wu Yvonne W, Gonzalez Fernando F
Department of Neurology, University of California, San Francisco, CA, USA; Department of Pediatrics, University of California, San Francisco, CA, USA.
Dev Med Child Neurol. 2015 Apr;57 Suppl 3:34-9. doi: 10.1111/dmcn.12730.
Perinatal hypoxic-ischaemic encephalopathy (HIE) occurs in 1 to 3 per 1000 term births. HIE is not preventable in most cases, and therapies are limited. Hypothermia improves outcomes and is the current standard of care. Yet, clinical trials suggest that 44-53% of infants who receive hypothermia will die or suffer moderate to severe neurological disability. In this article, we review the preclinical and clinical evidence for erythropoietin (EPO) as a potential novel neuroprotective agent for the treatment of HIE. EPO is a novel neuroprotective agent, with remarkable neuroprotective and neuroregenerative effects in animals. Rodent and primate models of neonatal brain injury support the safety and efficacy of multiple EPO doses for improving histological and functional outcomes after hypoxia-ischaemia. Small clinical trials of EPO in neonates with HIE have also provided evidence supporting safety and preliminary efficacy in humans. There is currently insufficient evidence to support the use of high-dose EPO in newborns with HIE. However, several on-going trials will provide much needed data regarding the safety and efficacy of this potential new therapy when given in conjunction with hypothermia for HIE. Novel neuroprotective therapies are needed to further reduce the rate and severity of neurodevelopmental disabilities resulting from HIE. High-dose EPO is a promising therapy that can be administered in conjunction with hypothermia. However, additional data are needed to determine the safety and efficacy of this adjuvant therapy for HIE.
围产期缺氧缺血性脑病（HIE）在每1000例足月分娩中发生率为1至3例。大多数情况下，HIE无法预防，治疗方法也有限。低温治疗可改善预后，是目前的标准治疗方法。然而，临床试验表明，接受低温治疗的婴儿中有44%至53%会死亡或遭受中度至重度神经残疾。在本文中，我们综述了促红细胞生成素（EPO）作为治疗HIE潜在新型神经保护剂的临床前和临床证据。EPO是一种新型神经保护剂，在动物中具有显著的神经保护和神经再生作用。新生儿脑损伤的啮齿动物和灵长类动物模型支持多次给予EPO剂量对改善缺氧缺血后组织学和功能结局的安全性和有效性。EPO在患有HIE的新生儿中的小型临床试验也提供了支持其在人类中的安全性和初步有效性的证据。目前尚无足够证据支持在患有HIE的新生儿中使用高剂量EPO。然而，几项正在进行的试验将提供关于这种潜在新疗法与HIE低温治疗联合使用时的安全性和有效性的急需数据。需要新的神经保护疗法来进一步降低HIE导致的神经发育障碍的发生率和严重程度。高剂量EPO是一种有前景的疗法，可与低温治疗联合使用。然而，需要更多数据来确定这种辅助疗法对HIE的安全性和有效性。
