Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia
Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia
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DOI：
10.1016/j.nbd.2005.09.008
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发表时间：
2006-03-01
影响因子：
6.1
通讯作者：
Kirik, D
中科院分区：
文献类型：
--
作者：
Carlsson, T;Winkler, C;Kirik, D
在最近的两项双盲临床试验中，胎儿腹侧中脑细胞移植到帕金森病（PD）患者的纹状体中，有很大比例的移植患者出现了运动障碍的副作用，这在假手术患者中未见。在其中一项试验中，运动障碍和非运动障碍移植患者之间的比较表明，纹状体神经再支配的不均匀模式可能是运动障碍的主要原因。在这里，我们研究的重要性，移植物放置的发展运动障碍帕金森病大鼠。每天注射左旋多巴6周，诱导PD患者出现类似峰值剂量运动障碍的异常不自主运动。运动障碍动物接受约130.000个胎儿腹侧中脑细胞作为单个移植物放置在纹状体头部的吻侧或尾侧。结果表明，移植物放置在尾部，但不是喙部，有效地减少左旋多巴诱导的肢体和口舌运动障碍，主要表现为运动过度。然而，同样的移植物，也诱导了一种新的类型的运动障碍的行为后，激活安非他明，这是没有看到在非移植病变对照。这些异常的不自主运动的严重程度显着相关，与较高的移植衍生的多巴胺能神经再支配的纹状体头部的尾部方面相对于喙部。结果表明，移植物诱导的运动障碍PD患者可能与单一的，小的移植物沉积，提供了一个不均匀的，斑片状的壳核神经再支配。(C)2005年爱思唯尔公司All rights reserved.
In two recent double-blind clinical trials of fetal ventral mesencephalic cell transplants into the striatum in patients with Parkinson's disease (PD), a significant proportion of the grafted patients developed dyskinetic side effects, which were not seen in the sham operated patients. Comparison between dyskinetic and non-dyskinetic grafted patients in one of the trials suggested that an uneven pattern of striatal reinnervation might be the leading cause of the dyskinesias. Here, we studied the importance of graft placement for the development of dyskinesias in parkinsonian rats. Abnormal involuntary movements resembling peak-dose dyskinesias seen in PD patients were induced by daily injections of L-DOPA for 6 weeks. The dyskinetic animals received about 130.000 fetal ventral mesencephalic cells as single grafts placement in the rostral or the caudal aspect of the head of striatum. The results show that grafts placed in the caudal, but not the rostral, part are effective in reducing the L-DOPA-induced limb and orolingual dyskinesia, predominantly seen as hyperkinesia. The same grafts, however, also induced a new type of dyskinetic behavior after activation with amphetamine, which were not seen in non-grafted lesion controls. The severity of these abnormal involuntary movements was significantly correlated with a higher graft-derived dopaminergic reinnervation in the caudal aspect of the head of striatum relative to the rostral part. The results indicate that graft-induced dyskinesias in PD patients may be linked to single, small graft deposits that provide an uneven, patchy reinnervation of the putamen. (C) 2005 Elsevier Inc. All rights reserved.