Keswani Sanjay C, Buldanlioglu Ulas, Fischer Angela, Reed Nicole, Polley Michelle, Liang Hong, Zhou Chunhua, Jack Christelene, Leitz Gerhard J, Hoke Ahmet
Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD, USA.
Ann Neurol. 2004 Dec;56(6):815-26. doi: 10.1002/ana.20285.
Clinically relevant peripheral neuropathies (such as diabetic and human immunodeficiency virus sensory neuropathies) are characterized by distal axonal degeneration, rather than neuronal death. Here, we describe a novel, endogenous pathway that prevents axonal degeneration. We show that in response to axonal injury, periaxonal Schwann cells release erythropoietin (EPO), which via EPO receptor binding on neurons, prevents axonal degeneration. We demonstrate that the relevant axonal injury signal that stimulates EPO production from surrounding glial cells is nitric oxide. In addition, we show that this endogenous pathway can be therapeutically exploited by administering exogenous EPO. In an animal model of distal axonopathy, systemic EPO administration prevents axonal degeneration, and this is associated with a reduction in limb weakness and neuropathic pain behavior. Our in vivo and in vitro data suggest that EPO prevents axonal degeneration and therefore may be therapeutically useful in a wide variety of human neurological diseases characterized by axonopathy.
临床相关的周围神经病变（如糖尿病性和人类免疫缺陷病毒感染所致的感觉神经病变）的特征是远端轴突变性，而非神经元死亡。在此，我们描述了一种防止轴突变性的新型内源性途径。我们发现，轴突损伤时，轴周雪旺细胞会释放促红细胞生成素（EPO），其通过与神经元上的EPO受体结合来防止轴突变性。我们证明，刺激周围神经胶质细胞产生EPO的相关轴突损伤信号是一氧化氮。此外，我们表明，通过给予外源性EPO可对这种内源性途径进行治疗性利用。在远端轴突病动物模型中，全身性给予EPO可防止轴突变性，这与肢体无力和神经性疼痛行为的减轻有关。我们的体内和体外数据表明，EPO可防止轴突变性，因此可能对多种以轴突病为特征的人类神经系统疾病具有治疗作用。
