Love R M, Branton R L, Karlsson J, Brundin P, Clarke D J
Department of Human Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
Cell Transplant. 2002;11(7):653-62. doi: 10.3727/000000002783985431.
The effect of pretreating cell suspensions of embryonic rat ventral mesencephala (VM) with antioxidant combinations on the survival of dopaminergic (DA) neurons was studied in vitro and following transplantation into the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease. The in vitro experiments examined the effects of two thiol antioxidants, N-acetyl-L-cysteine (NAC) and reduced glutathione (GSH), and a member of the lazaroid family of 21-aminosteroids, U-83836E, singly and in combination, on survival of DA neurons derived from dissociated E14 rat VM tissue. For in vivo studies, cell suspensions were pretreated with combinations of NAC, GSH, and U-83836E prior to transplanting into 6-OHDA-lesioned rats to investigate whether DA neuron survival could be further improved. NAC, GSH, and U-83836E individually increased DA neuron survival in vitro and a combination of all three resulted in the greatest survival. In vivo, pretreatment with U-83836E alone resulted in a significantly greater reduction in amphetamine-induced rotation 6 weeks postgrafting compared with a control group receiving nontreated graft tissue. This functional effect correlated with a significant improvement in DA neuron survival 6 weeks postgrafting. The thiol combination pretreatment of NAC and GSH, and the triple combination of NAC, GSH, and U-83836E, however, failed to improve both functional recovery and DA neuron survival when compared with the nontreated control grafts.
研究了用抗氧化剂组合预处理胚胎大鼠腹侧中脑（VM）细胞悬液对多巴胺能（DA）神经元存活的影响，实验分为体外实验以及将细胞悬液移植到单侧6-羟基多巴胺（6-OHDA）损伤的帕金森病大鼠模型后的实验。体外实验研究了两种硫醇抗氧化剂N-乙酰-L-半胱氨酸（NAC）和还原型谷胱甘肽（GSH），以及21-氨基类固醇类拉扎罗类药物家族的成员U-83836E单独使用和联合使用时，对源自E14大鼠VM组织解离后的DA神经元存活的影响。对于体内研究，在将细胞悬液移植到6-OHDA损伤的大鼠之前，先用NAC、GSH和U-83836E的组合进行预处理，以研究DA神经元的存活是否能进一步提高。NAC、GSH和U-83836E单独使用时均可提高体外DA神经元的存活率，三者联合使用时存活率最高。在体内，与接受未处理移植组织的对照组相比，单独用U-83836E预处理在移植后6周导致苯丙胺诱导的旋转显著降低。这种功能效应与移植后6周DA神经元存活率的显著提高相关。然而，与未处理的对照移植物相比，NAC和GSH的硫醇组合预处理以及NAC、GSH和U-83836E的三联组合未能改善功能恢复和DA神经元存活。
