Shimizu K, Tsuda N, Matsui Y, Okamoto Y, Miyao Y, Yamada M, Ikeda T, Hatanaka H, Mogami H
Department of Neurosurgery, Osaka University Medical School, Japan.
No To Shinkei. 1988 Jul;40(7):623-8.
Attempts to reconstruct the damaged nigrostriatal pathway in experimental models of Parkinson disease have thus far been carried out in animals with neurotoxically induced dopamine deficiency. Our study established that unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal-dopamine (DA) neurons produced a well-characterized functional asymmetry in the behavior of C57BL/6 (H-2b) mice. The intraperitoneal administration of methamphetamine induced ipsilateral rotation at 7-20 turns/min. 11 x 10(6) syngenic DA-rich cells of embryonic ventral mesencephalon were stereotaxically transplanted in the caudate-putamen. A complete recovery of methamphetamine-induced rotational response was produced around the 60-th day after the syngenic cell suspension graft. And a complete compensation of the rotational response was also brought about with the DA-rich cells from embryonic ventral mesencephalon (crown-rump length; 10-13 mm) of allogenic C 3 H/HeN (H-2k) mice. The FACS IV analysis revealed no H-2 (Kk and Iak) antigens before transplantation of these embryonic cells. Immunohistochemistry showed that the dopaminergic fibers had grown predominantly into the ipsilateral caudate-putamen. These results provide evidence of integration of syngenic and allogenic grafts and host tissue. And the immunological response in the transplanted brain are under investigation.
迄今为止，在帕金森病实验模型中重建受损黑质纹状体通路的尝试，都是在多巴胺因神经毒性而缺乏的动物身上进行的。我们的研究表明，黑质纹状体多巴胺（DA）神经元的单侧6-羟基多巴胺（6-OHDA）损伤，在C57BL/6（H-2b）小鼠的行为中产生了一种特征明确的功能不对称。腹腔注射甲基苯丙胺会诱导同侧以7至20转/分钟的速度旋转。将11×10⁶个同基因富含DA的胚胎腹侧中脑细胞立体定向移植到尾状核-壳核中。在同基因细胞悬液移植后约第60天，甲基苯丙胺诱导的旋转反应完全恢复。来自同种异体C3H/HeN（H-2k）小鼠胚胎腹侧中脑（冠臀长10至13毫米）的富含DA的细胞也能使旋转反应得到完全补偿。流式细胞仪IV分析显示，在这些胚胎细胞移植前未检测到H-2（Kk和Iak）抗原。免疫组织化学显示，多巴胺能纤维主要生长到同侧尾状核-壳核中。这些结果为同基因和异基因移植物与宿主组织的整合提供了证据。目前正在研究移植脑中的免疫反应。
