Fiandaca M S, Kordower J H, Hansen J T, Jiao S S, Gash D M
Department of Neurobiology and Anatomy, University of Rochester School of Medicine, New York 14642.
Exp Neurol. 1988 Oct;102(1):76-91. doi: 10.1016/0014-4886(88)90080-5.
Questions arising from recent clinical neural transplantation trials in Parkinson's disease have under-scored the necessity for a thorough experimental evaluation of the structural and functional consequences of this procedure. The present study investigated the neuroanatomical host reaction to intrastriatal implants in normal and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-treated nonhuman primates. Nine monkeys (Cebus apella) received intrastriatal implants using either a stereotactic approach with a silver tissue carrier or an open microsurgical procedure. Seven of these animals received intrastriatal adrenal medullary autografts, while two received control implants consisting of the tissue carrier alone. One month following transplantation, the hosts' brains were evaluated via immunohistochemical and routine histologic methods. In both MPTP-treated and normal monkeys, enhanced ipsilateral expression of tyrosine hydroxylase-like immunoreactive (TH-IR) fibers in the caudate nucleus was observed, despite minimal survival of adrenal chromaffin cells in the implants. The intensity of this response was greatest adjacent to the implant site, but a clearly increased degree of ipsilateral striatal fiber staining also could be seen several millimeters from the graft. TH-IR fibers also were more dense and of thicker caliber throughout the nigrostriatal and mesolimbic pathways ipsilateral to the implant. Control stereotactic implants, consisting of a silver tissue carrier alone, produced a similar enhancement of immunoreactive fibers, suggesting an induction of TH-IR fibers by the parenchymal injury produced during surgical implantation. There are two major hypotheses proposed to explain why adrenal medullary grafts may promote functional recovery in human parkinsonism: (1) replacement of lost striatal neurotransmitter (dopamine) by the viable grafted tissue, or (2) induction of recovery of remaining host dopaminergic systems by the implantation procedure. Our current data appear to support the latter.
近期帕金森病临床神经移植试验引发的问题凸显了对该手术的结构和功能后果进行全面实验评估的必要性。本研究调查了正常和经1-甲基-4-苯基-1,2,5,6-四氢吡啶（MPTP）处理的非人灵长类动物纹状体内植入物的神经解剖学宿主反应。9只猴子（僧帽猴）采用立体定向方法并使用银组织载体或开放式显微手术进行纹状体内植入。其中7只动物接受纹状体内肾上腺髓质自体移植，而2只接受仅由组织载体组成的对照植入物。移植后1个月，通过免疫组织化学和常规组织学方法评估宿主大脑。在MPTP处理的猴子和正常猴子中，尽管植入物中的肾上腺嗜铬细胞存活率极低，但在尾状核中观察到同侧酪氨酸羟化酶样免疫反应性（TH-IR）纤维表达增强。这种反应的强度在植入部位附近最大，但在距移植物几毫米处也可见同侧纹状体纤维染色程度明显增加。TH-IR纤维在植入物同侧的整个黑质纹状体和中脑边缘通路中也更密集且管径更粗。仅由银组织载体组成的对照立体定向植入物产生了类似的免疫反应性纤维增强，表明手术植入期间产生的实质损伤诱导了TH-IR纤维。有两个主要假说来解释为什么肾上腺髓质移植可能促进人类帕金森病的功能恢复：（1）存活的移植组织替代丢失的纹状体神经递质（多巴胺），或（2）植入程序诱导剩余宿主多巴胺能系统恢复。我们目前的数据似乎支持后者。
