Baker K A, Sadi D, Hong M, Mendez I
Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada.
J Comp Neurol. 2000 Oct 9;426(1):106-16.
The current transplantation strategy in experimental and clinical Parkinson's disease (PD) has been to place nigral dopaminergic grafts not in their ontogenic site (substantia nigra) but in their target area (striatum). Although intrastriatal dopaminergic grafts are capable of reinnervating the striatum, they fail to reinnervate the nigra, which may be an important factor limiting the efficacy of fetal tissue transplantation in parkinsonian patients. We have previously shown that simultaneous intrastriatal and intranigral dopaminergic grafts (double grafts) may provide a more complete restoration of the nigrostriatal circuitry (Mendez et al. [1996] J Neurosci 16:7216-7227; Mendez and Hong [1997] Brain Res 778:194-205). In the present study, we investigated the contribution of the intranigral graft to functional recovery in double-grafted hemiparkinsonian rats. Twenty Wistar rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway were divided into two groups and received either double grafts (n = 10) or intrastriatal grafts alone (n = 10). Following transplantation, both intrastriatally and double-grafted animals had a significant decrease in rotational behavior. However, only animals with double grafts exhibited a significant increase in contralateral adjusting step performance. The intranigral graft was subsequently lesioned by a second 6-OHDA injection. Following the second lesion, animals with double grafts exhibited a significant reversal of rotational behavior and a 51% reduction in contralateral adjusting step performance. The reversal in functional recovery correlated with a significant loss of intranigral grafted neurons. These results suggest that the intranigral graft has an important role in the functional recovery of double-grafted animals. Restoration of dopaminergic innervation to both the nigra and the striatum may be crucial for optimizing graft efficacy and may be a superior strategy in neural transplantation for PD.
目前在实验性和临床帕金森病（PD）中的移植策略是将黑质多巴胺能移植物植入其靶区（纹状体）而非其发生部位（黑质）。尽管纹状体内多巴胺能移植物能够重新支配纹状体，但它们无法重新支配黑质，这可能是限制帕金森病患者胎儿组织移植疗效的一个重要因素。我们之前已经表明，同时进行纹状体内和黑质内多巴胺能移植（双重移植）可能会更完整地恢复黑质纹状体回路（门德斯等人[1996年]《神经科学杂志》16:7216 - 7227；门德斯和洪[1997年]《脑研究》778:194 - 205）。在本研究中，我们调查了黑质内移植物对双重移植的偏侧帕金森病大鼠功能恢复的贡献。20只黑质纹状体通路单侧6 - 羟基多巴胺（6 - OHDA）损伤的Wistar大鼠被分为两组，分别接受双重移植（n = 10）或仅纹状体内移植（n = 10）。移植后，纹状体内移植和双重移植的动物旋转行为均显著减少。然而，只有双重移植的动物对侧调整步表现有显著增加。随后通过第二次6 - OHDA注射损伤黑质内移植物。第二次损伤后，双重移植的动物旋转行为显著逆转，对侧调整步表现降低了51%。功能恢复的逆转与黑质内移植神经元的显著丢失相关。这些结果表明黑质内移植物在双重移植动物的功能恢复中起重要作用。恢复黑质和纹状体的多巴胺能神经支配对于优化移植物疗效可能至关重要，并且可能是帕金森病神经移植的一种更优策略。
