Department of Stereotactic and Functional Neurosurgery, Laboratory of Molecular Neurosurgery, Neurocentre, University Hospital, Breisacher Strasse 64, 79106 Freiburg, Germany.
Exp Cell Res. 2012 Dec 10;318(20):2531-42. doi: 10.1016/j.yexcr.2012.08.002. Epub 2012 Aug 27.
Neural transplantation in experimental parkinsonism (PD) is limited by poor survival of grafted embryonic dopaminergic (DA) cells. In this proof-of-principle study we hypothesized that a first regular initial graft may create a "dopaminergic" environment similar to the perinatal substantia nigra and consequently stimulate a subsequent graft. Therefore, we grafted ventral mesencephalic neurons sequentially at different time intervals into the same target localization. Rats with a unilateral lesion of the dopamine neurons produced by injections of 6-hydroxydopamine (6-OHDA) received E14 ventral mesencephalon derived grafts into the DA-depleted striatum. In the control group we grafted all 6 deposits on the first day (d0). The other 4 groups received four graft deposits distributed over 2 implantation tracts followed by a second engraftment injected into the same site 3, 6, 14 and 21 days later. Quantitative assessment of the survival of tyrosine hydroxylase-immunoreactive neurons and graft volume revealed best results for those DA grafts implanted 6 days after the first one. In the present study, a model of short-interval sequential transplantation into the same target-site, so called "nest" grafts were established in the 6-OHDA rat model of PD which might become a useful tool to further elucidate the close neurotrophic and neurotopic interactions between the immediate graft vicinity and the cell suspension graft. In addition, we could show that the optimal milieu was established around the sixth day after the initial transplantation. This may also help to further optimize current transplantation strategies to restore the DA system in patients with PD.
实验性帕金森病（PD）中的神经移植受到移植胚胎多巴胺能（DA）细胞存活率低的限制。在这项原理验证研究中，我们假设初次常规移植可能会产生类似于围产期黑质的“多巴胺能”环境，并因此刺激随后的移植。因此，我们在不同的时间间隔将腹侧中脑神经元顺序移植到相同的靶位。通过注射 6-羟多巴胺（6-OHDA）导致多巴胺神经元损伤的大鼠接受源自 E14 腹侧中脑的移植物，移植到 DA 耗竭纹状体中。在对照组中，我们在第一天（d0）移植了所有 6 个移植物。其余 4 组在 2 个植入道中分布了 4 个移植物，然后在第 3、6、14 和 21 天再次将同一部位注射第二支移植物。酪氨酸羟化酶免疫反应性神经元存活和移植物体积的定量评估显示，初次移植后 6 天植入的 DA 移植物效果最佳。在本研究中，在 PD 的 6-OHDA 大鼠模型中建立了一种短时间间隔的顺序移植到同一靶位的模型，即所谓的“巢”移植，它可能成为进一步阐明即时移植部位附近和细胞悬浮移植之间密切的神经营养和神经位相互作用的有用工具。此外，我们还表明，在初次移植后的第六天左右建立了最佳环境。这也可能有助于进一步优化当前的移植策略，以恢复 PD 患者的 DA 系统。
