Chatagner A, Hüppi P S, Ha-Vinh Leuchter R, Sizonenko S
Service du développement et de la croissance, Département de l'enfant et de l'adolescence, Hôpitaux Universitaires de Genève, Suisse.
Arch Pediatr. 2010 Sep;17 Suppl 3:S78-84. doi: 10.1016/S0929-693X(10)70905-2.
Erythropoietin (Epo) has long been recognised for its role in the control of erythropoiesis and therefore in the treatment of anemia including anemia of prematurity. The erythropoietin receptor (Epo-R) though is expressed in many other organs including the CNS. This review focuses on the role of erythropoietin during the development of the CNS and its potential role as a neuroprotective agent. Epo-R is expressed in many different cellules of the CNS during development including neural progenitor cells, neurons, astrocytes and oligodendrocytes. In the event of hypoxia CNS cells respond with increase of erythropoietin release with subsequent stimulation of neurogenesis through Epo-R on neural progenitor cells. In an Epo-R knock-out model therefore cerebral development is severely impaired. In models of hypoxia-ischemia exogenous Epo has been shown to reduce lesion size and improve structural and functional recovery. Human studies are emerging using Epo as a neuroprotective agent both for the term infant with hypoxia-ischemia as well as for the extremely preterm infant.
长期以来,促红细胞生成素(Epo)在控制红细胞生成以及治疗包括早产儿贫血在内的贫血方面的作用已得到认可。然而,促红细胞生成素受体(Epo - R)在包括中枢神经系统(CNS)在内的许多其他器官中也有表达。本综述重点关注促红细胞生成素在中枢神经系统发育过程中的作用及其作为神经保护剂的潜在作用。在发育过程中,Epo - R在中枢神经系统的许多不同细胞中表达,包括神经祖细胞、神经元、星形胶质细胞和少突胶质细胞。在缺氧情况下,中枢神经系统细胞会通过增加促红细胞生成素的释放做出反应,随后通过神经祖细胞上的Epo - R刺激神经发生。因此,在Epo - R基因敲除模型中,脑发育会严重受损。在缺氧缺血模型中,外源性Epo已被证明可减小损伤大小并改善结构和功能恢复。关于将Epo用作神经保护剂的人体研究正在兴起,用于治疗足月缺氧缺血性婴儿以及极早产儿。