Cordeiro Karina Kohn, Cordeiro Joacir Graciolli, Furlanetti Luciano Lopes, Garcia Salazar Joanna Alejandra, Tenório Sérgio Bernardo, Winkler Christian, Döbrössy Máté Daniel, Nikkhah Guido
Department of Stereotactic and Functional Neurosurgery, Laboratory of Stereotaxy and Interventional Neurosciences, University Freiburg-Medical Center, Breisacher Str. 64, Freiburg, 79106, Germany; Federal University of Paraná, Hospital de Clínicas, Curitiba, Brazil.
Eur J Neurosci. 2014 May;39(9):1474-84. doi: 10.1111/ejn.12541. Epub 2014 Mar 14.
Subthalamic nucleus (STN) modulation is currently the gold standard in the treatment of Parkinson's disease (PD) cases refractory to medication. Cell transplantation is a tissue-restorative approach and is a promising strategy in the treatment of PD. One of the obstacles to overcome in cell therapy is the poor dopaminergic cell survival. Our experiment investigates the impact of a partial subthalamotomy prior to ventral mesencephalic (VM) embryonic cell transplantation on dopaminergic cell survival and functional outcome. Unilateral dopamine depletion was carried out in rats, via medial forebrain bundle (MFB) injection of 6-hydroxydopamine, and half of the animals went on to receive unilateral excitotoxic lesions of the STN/Zone Incerta (ZI) causing partial lesion of these structures on the same side as the MFB lesion. All MFB-lesioned animals, with or without the STN/ZI lesion, received striatal ipsilateral embryonic VM cell grafts. The data suggest that the STN/ZI lesion could boost the dopamine cell survival in the grafts by 2.6-fold compared with the control grafted-only group. Moreover, performance on the drug-induced rotation and the spontaneous behavior tests were ameliorated on the STN/ZI-lesioned group to a significantly greater extent than the grafted-only group. These data suggest that the STN/ZI partial lesion optimized the striatal environment, promoting an improvement in cell survival. Further studies are needed to see whether the synergy between STN modulation via deep brain stimulation and cell therapy might have clinical applications in the management of PD.
丘脑底核（STN）调制目前是治疗对药物难治的帕金森病（PD）病例的金标准。细胞移植是一种组织修复方法，是治疗PD的一种有前景的策略。细胞治疗中需要克服的障碍之一是多巴胺能细胞存活率低。我们的实验研究了腹侧中脑（VM）胚胎细胞移植前部分丘脑底核切开术对多巴胺能细胞存活和功能结果的影响。通过内侧前脑束（MFB）注射6-羟基多巴胺在大鼠中进行单侧多巴胺耗竭，并且一半的动物继续接受STN/未定带（ZI）的单侧兴奋性毒性损伤，导致这些结构在与MFB损伤同侧的部分损伤。所有MFB损伤的动物，无论有无STN/ZI损伤，均接受纹状体同侧胚胎VM细胞移植。数据表明，与仅移植对照组相比，STN/ZI损伤可使移植中的多巴胺细胞存活率提高2.6倍。此外，STN/ZI损伤组在药物诱导旋转和自发行为测试中的表现改善程度明显大于仅移植组。这些数据表明，STN/ZI部分损伤优化了纹状体环境，促进了细胞存活的改善。需要进一步研究以确定通过深部脑刺激进行的STN调制与细胞治疗之间的协同作用是否可能在PD的管理中具有临床应用。
