Schumacher J M, Hantraye P, Brownell A L, Riche D, Madras B K, Davenport P D, Maziere M, Elmaleh D R, Brownell G L, Isacson O
Department of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
Cell Transplant. 1992;1(4):313-22. doi: 10.1177/096368979200100409.
In this article, we show that 1) computed tomographic (CT)-guided stereotactic infusion of an excitotoxin into the striatum of a nonhuman primate provides a useful neuropathologic and behavioral model for Huntington's disease. 2) High-resolution positron emission tomography (PET) can be used to image the decreased glucose utilization and the preservation of dopaminergic terminals in the lesioned striatum by using 2-fluoro-deoxy-D-glucose (2FDG) and N-(C-11)-methyl-2-beta-carbomethoxy-3-beta-phenyl tropane (CPT) as tracers. 3) Transplantation of cross-species striatal fetal tissue into the lesioned caudate-putamen reduces many of the abnormal motor movements and behavioral changes seen in the Huntington's disease primate model. 4) Graft rejection results in the return of the abnormal signs of the pregrafted state. These results indicate that treatment of the neuronal deficit in Huntington's disease can involve intervention at the local neuronal circuit level. CT-guided stereotactic implantation of cells that might protect or replace this defective circuitry may eventually provide an effective treatment for Huntington's disease.
在本文中，我们表明：1）在非人类灵长类动物的纹状体中，计算机断层扫描（CT）引导下向其注入兴奋性毒素可提供一种用于亨廷顿病的有用的神经病理学和行为学模型。2）高分辨率正电子发射断层扫描（PET）可通过使用2-氟-脱氧-D-葡萄糖（2FDG）和N-（C-11）-甲基-2-β-甲氧基-3-β-苯基托烷（CPT）作为示踪剂，对病变纹状体中葡萄糖利用的减少和多巴胺能终末的保留进行成像。3）将跨物种的纹状体胎儿组织移植到病变的尾状核-壳核中，可减少在亨廷顿病灵长类动物模型中观察到的许多异常运动和行为变化。4）移植物排斥导致移植前状态的异常体征再次出现。这些结果表明，对亨廷顿病神经元缺陷的治疗可能涉及在局部神经元回路水平进行干预。CT引导下立体定向植入可能保护或替代这种有缺陷回路的细胞，最终可能为亨廷顿病提供一种有效的治疗方法。
