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Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia.

机译:纹状体中的移植物放置和不均匀的神经支配模式对于移植物诱导的运动障碍的发展是重要的。

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摘要

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.
机译:在最近的两项帕金森氏病(PD)患者将胎儿腹侧中脑细胞移植到纹状体的双盲临床试验中,很大一部分移植患者出现了运动障碍性副作用,这在假手术患者中没有发现。在一项试验中比较运动障碍和非运动障碍患者的情况表明,纹状体神经支配方式的不均匀可能是运动障碍的主要原因。在这里,我们研究了移植放置对帕金森病大鼠运动障碍发展的重要性。每天注射L-DOPA达6周,可诱发在PD患者中出现的类似于峰值剂量运动障碍的异常非自愿运动。运动障碍的动物在纹状体头部的头侧或尾侧以单个移植物的形式接受了约130.000个胎儿腹中脑细胞。结果表明,放置在尾部而不是延髓部的移植物可有效减轻L-DOPA引起的肢体和口语运动障碍,主要是运动亢进。然而,相同的移植物在用苯丙胺激活后也诱导了一种新型的运动障碍行为,这在未移植的病灶对照中没有发现。这些异常的不自主运动的严重程度与纹状体头部尾端相对于延髓部较高的移植物衍生的多巴胺能神经支配显着相关。结果表明,PD患者的移植物诱发的运动障碍可能与单个的小移植物沉积物有关,这些沉积物提供了不均匀的斑状神经支配神经。

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