Juul S
Department of Pediatrics, Division of Neonatology, University of Washington, Seattle, Washington 98195, USA.
Acta Paediatr Suppl. 2002;91(438):36-42. doi: 10.1111/j.1651-2227.2002.tb02904.x.
A new field of clinical and scientific interest has recently developed based on the discovery that the hematopoietic cytokine erythropoietin (Epo) has important non-hematopoietic functions in the brain and other organs, particularly during development. The biological effects of Epo in the central nervous system (CNS) involve activation of its specific receptor and corresponding signal transduction pathways. Epo receptor expression is abundant in the developing mammalian brain, and decreases as term approaches. Epo has been identified as a neurotrophic and neuroprotective agent in a wide variety of experimental paradigms, from neuronal cell culture to in vivo models of brain injury. Several mechanisms by which Epo produces neuroprotection are recognized. Epo (i) decreases glutamate toxicity, (ii) induces the generation of neuronal anti-apoptotic factors, (iii) reduces inflammation, (iv) decreases nitric oxide-mediated injury, and (v) has direct antioxidant effects.
Collectively, the evidence suggests that Epo may provide a new approach to the treatment of a variety of CNS disorders in adults and children, especially as a possible therapy for perinatal asphyxia. This review summarizes the current knowledge on the neurotrophic and neuroprotective functions of Epo in the developing and injured brain.
基于造血细胞因子促红细胞生成素(Epo)在脑和其他器官中具有重要的非造血功能这一发现,尤其是在发育过程中,最近出现了一个新的临床和科学研究领域。Epo在中枢神经系统(CNS)中的生物学效应涉及其特异性受体的激活及相应的信号转导途径。Epo受体在发育中的哺乳动物脑中表达丰富,并随着足月临近而减少。在从神经元细胞培养到脑损伤体内模型的各种实验范式中,Epo已被确定为一种神经营养和神经保护剂。人们认识到Epo产生神经保护作用的几种机制。Epo(i)降低谷氨酸毒性,(ii)诱导神经元抗凋亡因子的产生,(iii)减轻炎症,(iv)减少一氧化氮介导的损伤,以及(v)具有直接的抗氧化作用。
总体而言,证据表明Epo可能为治疗成人和儿童的多种CNS疾病提供一种新方法,尤其是作为围产期窒息的一种可能治疗方法。本综述总结了目前关于Epo在发育中和受损脑中的神经营养和神经保护功能的知识。