Ahlskog J E, Kelly P J, van Heerden J A, Stoddard S L, Tyce G M, Windebank A J, Bailey P A, Bell G N, Blexrud M D, Carmichael S W
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
Mayo Clin Proc. 1990 Mar;65(3):305-28. doi: 10.1016/s0025-6196(12)62532-4.
Transplantation of adrenal medulla into the caudate nucleus as treatment for Parkinson's disease was performed in eight patients. Although our previous 6-month follow-up revealed early modest improvement, an extension of that follow-up to 1 year disclosed no additional gains in any patient. At the end of 1 year, only one patient could be categorized as moderately improved; three patients were mildly improved, and four patients were unimproved. The rationale for transplanting adrenal medulla was to reestablish a physiologic source of dopamine to the striatum. We measured cerebrospinal fluid (CSF) and plasma catecholamines and metabolites before and after transplantation. Conjugated dopamine (the predominant form of dopamine found in the CSF) and homovanillic acid (the major dopamine metabolite) were modestly and inconsistently increased in the CSF. Conjugated and free epinephrine and norepinephrine, as well as 3-methoxy-4-hydroxyphenylglycol concentrations were not increased in CSF after graft placement, an indication that the adrenal chromaffin cells were no longer producing high levels of these nondopamine catecholamines and metabolites. CSF cortisol concentrations were not increased after transplantation, compared with values from controls, consistent with low numbers of functioning adrenal cortical cells contaminating the graft (or poor survival). Posttransplantation CSF did not induce a neurotrophic effect in cell cultures of 15-day embryonic rat dorsal root ganglion or PC12 (rat pheochromocytoma) cell lines. Survival of samples of patients' adrenal medullary tissue for 2 weeks in tissue culture attested to the viability of the graft at the time of transplantation. The relative concentrations of dopamine to epinephrine or norepinephrine increased in these cultured adrenal medullary cells, presumably because of loss of the glucocorticoid influence on catecholamine synthesis. A wide variety of factors could have contributed to our failure to replicate the earlier impressive results of adrenal-to-brain transplantation reported by others. Continued transplantation studies in animal models of parkinsonism are necessary for better elucidation of these factors.
对8例帕金森病患者进行了肾上腺髓质移植到尾状核的治疗。尽管我们之前6个月的随访显示早期有适度改善，但将随访延长至1年发现，没有任何患者有进一步改善。在1年结束时，只有1例患者可归类为中度改善；3例患者轻度改善，4例患者无改善。移植肾上腺髓质的理论依据是为纹状体重新建立多巴胺的生理来源。我们在移植前后测量了脑脊液（CSF）和血浆儿茶酚胺及其代谢产物。结合多巴胺（CSF中发现的多巴胺的主要形式）和高香草酸（主要的多巴胺代谢产物）在CSF中适度且不一致地增加。移植后，CSF中结合和游离肾上腺素、去甲肾上腺素以及3-甲氧基-4-羟基苯乙二醇浓度未增加，这表明肾上腺嗜铬细胞不再产生高水平的这些非多巴胺儿茶酚胺及其代谢产物。与对照组相比，移植后脑脊液皮质醇浓度未增加，这与污染移植物的有功能的肾上腺皮质细胞数量少（或存活率低）一致。移植后的脑脊液在15天龄胚胎大鼠背根神经节或PC12（大鼠嗜铬细胞瘤）细胞系的细胞培养中未诱导神经营养作用。患者肾上腺髓质组织样本在组织培养中存活2周证明了移植时移植物的活力。这些培养的肾上腺髓质细胞中多巴胺与肾上腺素或去甲肾上腺素的相对浓度增加，可能是由于糖皮质激素对儿茶酚胺合成的影响丧失。多种因素可能导致我们未能重现其他人报道的早期令人印象深刻的肾上腺-脑移植结果。对帕金森病动物模型进行持续的移植研究对于更好地阐明这些因素是必要的。
