Przedborski S, Levivier M, Kostic V, Jackson-Lewis V, Dollison A, Gash D M, Fahn S, Cadet J L
Laboratory of Preclinical Neurosciences, Columbia University, College of Physicians and Surgeons, New York, New York 10032.
Brain Res. 1991 Jun 7;550(2):231-8. doi: 10.1016/0006-8993(91)91323-s.
Administration of the neurotoxin 6-hydroxydopamine (6-OHDA) to rat brain causes biochemical and neuroanatomical changes to the nigrostriatal dopaminergic pathway similar to those observed in Parkinson's disease (PD). Although the cause of PD is unknown, it has been hypothesized that the neurodegenerative changes seen in PD might result from exposure to a neurotoxin. Therefore, strategies for limiting neurotoxin-induced dopaminergic damages, like those caused by 6-OHDA, may be of both clinical and basic interest. Accordingly, we tested the ability of both fetal neural (striatum) and fetal non-neural (liver) tissue implants to protect the rat striatum against the toxic effects of a subsequent intrastriatal injection of 6-OHDA. Non-grafted rats (lesion only) showed amphetamine-induced rotational behavior and a decrease in striatal [3H]mazindol-labeled dopamine uptake sites after 6-OHDA injection. In contrast, the animals grafted with striatum or liver showed no behavioral or biochemical changes. Interestingly, sham-transplanted control animals were also protected against the 6-OHDA-induced toxicity. These results suggest that the resistance of the dopaminergic system against 6-OHDA neurotoxicity observed in grafted and sham-transplanted animals is likely to be related to the surgical procedure itself. This observation points to a possible role for surgery-related events in the clinical improvement described in PD patients who underwent intracerebral transplantation.
给大鼠脑内注射神经毒素6-羟基多巴胺（6-OHDA）会导致黑质纹状体多巴胺能通路发生生化和神经解剖学变化，类似于在帕金森病（PD）中观察到的变化。尽管PD的病因尚不清楚，但据推测，PD中出现的神经退行性变化可能是由于接触神经毒素所致。因此，限制神经毒素诱导的多巴胺能损伤（如6-OHDA所引起的损伤）的策略可能具有临床和基础研究价值。相应地，我们测试了胎儿神经组织（纹状体）和胎儿非神经组织（肝脏）植入物保护大鼠纹状体免受随后纹状体内注射6-OHDA毒性影响的能力。未移植的大鼠（仅损伤组）在注射6-OHDA后表现出苯丙胺诱导的旋转行为，纹状体内[3H]麦角吲哚标记的多巴胺摄取位点减少。相比之下，移植了纹状体或肝脏的动物没有行为或生化变化。有趣的是，假移植对照动物也受到保护，免受6-OHDA诱导的毒性影响。这些结果表明，在移植和假移植动物中观察到的多巴胺能系统对6-OHDA神经毒性的抗性可能与手术过程本身有关。这一观察结果指出，手术相关事件在接受脑内移植的PD患者所描述的临床改善中可能发挥作用。
