摘要
在过去的十年,重组人红细胞生成素(rhEPO)已经被誉为多种脑损伤疾病中的很好的治疗策略。中风动物模型实验的理想效果导致了迅速的临床试验,急速的进入到了II期试验。rhEPO 的多元神经保护形态未能平稳的转化成人脑缺血损伤,并且对新生儿提供有限的帮助。鉴于相反的结果,这种临床试验为什么和怎样失败的若干问题被提出。有来自初步研究指向光明未来的支撑证据。因此,本综述的目的就是未来解答这些问题,通过讨论已报到的对多种脑损伤动物模型有神经保护作用的rhEPO信号通路。检索了主要的生物医学文献数据库(MEDLINE、ISI、PubMed和Cochrane Library),使用红细胞生成素、中风、新生儿缺氧缺血、脑溢血等关键词。本文将讨论影响rhEPO治疗的混合因素,因此挑战它的临床可译性。最后,尽管rhEPO临床试验有许多缺点,但是如果持续小心的给药,它也许仍旧是新生儿的有希望的治疗剂代表。
关键词: 红细胞生成素信号,janus酪氨酸蛋白激酶2,信号转导和转录活化因子3
Current Medicinal Chemistry
Title:Erythropoietin in Stroke Therapy: Friend or Foe
Volume: 22 Issue: 10
Author(s): Rhonda Souvenir, Desislava Doycheva, John H Zhang and Jiping Tang
Affiliation:
关键词: 红细胞生成素信号,janus酪氨酸蛋白激酶2,信号转导和转录活化因子3
摘要: Recombinant human erythropoietin (rhEPO), over the past decade, was hailed as an auspicious therapeutic strategy for various types of brain injuries. The promising results from experiments conducted in animal models of stroke led to a hurried clinical trial that was swiftly aborted in Phase II. The multiple neuroprotective modalities of rhEPO failed to translate smoothly to human adult ischemic brain injury and provided limited aid to neonates. In light of the antithetical results, several questions were raised as to why and how this clinical trial failed. There was bolstering evidence from the preliminary studies that pointed to a bright future. Therefore, the objective of this review is to address these questions by discussing the signaling pathways of rhEPO that are reported to mediate the neuroprotective effect in various animal models of brain injury. Major biomedical bibliographical databases (MEDLINE, ISI, PubMed, and Cochrane Library) were searched with the use of keywords such as erythropoietin, stroke, neonatal hypoxia ischemia, intracerebral hemorrhage, etc. This article will discuss the confounding factors that influence the efficacy of rhEPO treatment hence challenging its clinical translatability. Lastly, rhEPO may still be a promising therapeutic candidate for neonates in spite of its shortcoming in clinical trial if caution is taken with the dose and duration of its administration.
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Cite this article as:
Rhonda Souvenir, Desislava Doycheva, John H Zhang and Jiping Tang , Erythropoietin in Stroke Therapy: Friend or Foe, Current Medicinal Chemistry 2015; 22 (10) . https://dx.doi.org/10.2174/0929867322666150114152134
DOI https://dx.doi.org/10.2174/0929867322666150114152134 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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