Yazdi A, Baharvand H, Javan M
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran.
Neuroscience. 2015 Dec 17;311:34-44. doi: 10.1016/j.neuroscience.2015.10.013. Epub 2015 Oct 17.
Multiple sclerosis (MS) is a chronic, progressive demyelinating disorder which affects the central nervous system (CNS) and is recognized as the major cause of nervous system disability in young adults. Enhancing myelin repair by stimulating endogenous progenitors is a main goal in efforts for MS treatment. Fingolimod (FTY720) which is administrated as an oral medicine for relapsing-remitting MS has direct effects on neural cells. In this study, we hypothesized if daily treatment with FTY720 enhances endogenous myelin repair in a model of local demyelination induced by lysolecithin (LPC). We examined the response of inflammatory cells as well as resident OPCs and evaluated the number of newly produced myelinating cells in animals which were under daily treatment with FTY720. FTY720 at doses 0.3 and 1mg/kg decreased the inflammation score at the site of LPC injection and decreased the extent of demyelination. FTY720 especially at the lower dose increased the number of remyelinated axons and newly produced myelinating cells. These data indicate that repetitive treatment with FTY720, behind an anti-inflammatory effect, exerts beneficial effects on the process of endogenous repair of demyelinating insults.
多发性硬化症（MS）是一种慢性进行性脱髓鞘疾病，会影响中枢神经系统（CNS），并被认为是导致年轻人神经系统残疾的主要原因。通过刺激内源性祖细胞来促进髓鞘修复是MS治疗研究的主要目标。作为治疗复发缓解型MS的口服药物，芬戈莫德（FTY720）对神经细胞有直接作用。在本研究中，我们假设每日给予FTY720是否能增强由溶血卵磷脂（LPC）诱导的局部脱髓鞘模型中的内源性髓鞘修复。我们检测了炎症细胞以及驻留少突胶质前体细胞（OPC）的反应，并评估了每日接受FTY720治疗的动物中新产生的髓鞘形成细胞的数量。剂量为0.3和1mg/kg的FTY720降低了LPC注射部位的炎症评分，并减轻了脱髓鞘程度。FTY720，尤其是较低剂量时，增加了重新髓鞘化轴突和新产生的髓鞘形成细胞的数量。这些数据表明，FTY720的重复治疗在具有抗炎作用的同时，对脱髓鞘损伤的内源性修复过程也产生有益影响。
