Shinotoh H, Snow B J, Hewitt K A, Pate B D, Doudet D, Nugent R, Perl D P, Olanow W, Calne D B
Neurodegenerative Disorders Centre, University of British Columbia, Vancouver, Canada.
Neurology. 1995 Jun;45(6):1199-204. doi: 10.1212/wnl.45.6.1199.
Using MRI and PET, we investigated the consequences of manganese intoxication in a primate model of parkinsonism and dystonia. Three rhesus monkeys were injected intravenously with doses of 10 to 14 mg/kg of MnCl2 on seven occasions, each a week apart. Two animals became hypoactive with abnormal extended posturing in the hind limbs. These motor disturbances did not improve with administration of levodopa. In all three monkeys, T1-weighted MRI demonstrated high signal intensities in the regions of the striatum, globus pallidus, and substantia nigra. No significant changes were found on [18F]6-fluoro-L-dopa, [11C]raclopride, or [18F]fluorodeoxyglucose PET. These results are consistent with the pathologic findings, which were primarily confined to the globus pallidus, and indicate that manganese intoxication is associated with preservation of the nigrostriatal dopaminergic pathway, despite clinical evidence of parkinsonian deficits. Chronic manganese intoxication may cause parkinsonism by damaging output pathways downstream to the nigrostriatal dopaminergic pathway. This is consistent with the demonstrated lack of therapeutic response to levodopa.
我们使用磁共振成像（MRI）和正电子发射断层扫描（PET）技术，在帕金森病和肌张力障碍的灵长类动物模型中研究了锰中毒的后果。三只恒河猴每周静脉注射一次剂量为10至14毫克/千克的氯化锰，共注射七次。两只动物出现活动减少，并伴有后肢异常伸展姿势。左旋多巴治疗后，这些运动障碍并未改善。在所有三只猴子中，T1加权MRI显示纹状体、苍白球和黑质区域信号强度增高。在[18F]6-氟-L-多巴、[11C]雷氯必利或[18F]氟脱氧葡萄糖PET检查中未发现明显变化。这些结果与主要局限于苍白球的病理发现一致，表明尽管有帕金森病缺陷的临床证据，但锰中毒与黑质纹状体多巴胺能通路的保留有关。慢性锰中毒可能通过损害黑质纹状体多巴胺能通路下游的输出通路而导致帕金森病。这与对左旋多巴缺乏治疗反应的结果一致。
