NEUROPATHOLOGICAL EVIDENCE OF GRAFT-SURVIVAL AND STRIATAL REINNERVATION AFTER THE TRANSPLANTATION OF FETAL MESENCEPHALIC TISSUE IN A PATIENT WITH PARKINSONS-DISEASE
NEUROPATHOLOGICAL EVIDENCE OF GRAFT-SURVIVAL AND STRIATAL REINNERVATION AFTER THE TRANSPLANTATION OF FETAL MESENCEPHALIC TISSUE IN A PATIENT WITH PARKINSONS-DISEASE
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DOI：
10.1056/nejm199504273321702
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发表时间：
1995-04-27
影响因子：
158.5
通讯作者：
OLANOW, CW
中科院分区：
文献类型：
--
作者：
KORDOWER, JH;FREEMAN, TB;OLANOW, CW
背景。正在进行试验以确定胎儿黑质移植物是否可以改善帕金森病患者的运动功能。一些研究使用正电子发射断层扫描 (PET) 上的氟多巴摄取作为移植物活力的标记，但氟多巴摄取并不能区分宿主神经元和移植神经元。目前还没有直接证据表明胎儿组织移植物可以存活并支配纹状体。方法。我们研究了一名患有晚期帕金森病的 59 岁男性，他接受了连合后壳核中胎儿腹侧中脑组织的双侧移植物。该组织来自受孕后 6 1/2 至 9 周之间的七个胚胎。 18 个月后，患者因严重肺栓塞死亡。使用酪氨酸羟化酶免疫组织化学方法对大脑进行研究。结果。移植后，患者的运动功能持续改善，PET 扫描显示壳核中氟多巴的摄取逐渐增加。在大脑检查中，每个大移植物似乎都是可行的。每个都整合到宿主纹状体中，并包含密集的多巴胺能神经元簇。这些神经元的突起从移植物中长出，并以斑块矩阵模式为纹状体提供广泛的多巴胺能神经支配，未移植的壳核区域显示出稀疏的多巴胺能神经支配。我们无法识别宿主多巴胺能过程的任何萌芽，结论。胎儿中脑组织的移植物可以在人脑中长期存活，并恢复帕金森病患者纹状体的多巴胺能神经支配。在我们研究的患者中，临床改善和 PET 扫描中氟多巴摄取的增强与移植物的存活和纹状体的多巴胺能神经支配有关。
Background. Trials are under way to determine whether fetal nigral grafts can improve motor function in patients with Parkinson's disease. Some studies use fluorodopa uptake on positron-emission tomography (PET) as a marker of graft viability, but fluorodopa uptake does not distinguish between host and grafted neurons. There has been no direct evidence that grafts of fetal tissue can survive and innervate the striatum.Methods. We studied a 59-year-old man with advanced Parkinson's disease who received bilateral grafts of fetal ventral mesencephalic tissue in the postcommissural putamen. The tissue came from seven embryos between 6 1/2 and 9 weeks after conception. The patient died 18 months later from a massive pulmonary embolism. The brain was studied with the use of tyrosine hydroxylase immunohistochemical methods.Results. After transplantation, the patient had sustained improvement in motor function and a progressive increase in fluorodopa uptake in the putamen on PET scanning, On examination of the brain, each of the large grafts appeared to be viable. Each was integrated into the host striatum and contained dense clusters of dopaminergic neurons. Processes from these neurons had grown out of the grafts and provided extensive dopaminergic reinnervation to the striatum in a patch-matrix pattern, Ungrafted regions of the putamen showed sparse dopaminergic innervation. We could not identify any sprouting of host dopaminergic processes,Conclusions. Grafts of fetal mesencephalic tissue can survive for a long period in the human brain and restore dopaminergic innervation to the striatum in patients with Parkinson's disease. In the patient we studied, clinical improvement and enhanced fluorodopa uptake on PET scanning were associated with the survival of the grafts and dopaminergic reinnervation of the striatum.