Functional and anatomical reconstruction of the 6-hydroxydopamine lesioned nigrostriatal system of the adult rat
Functional and anatomical reconstruction of the 6-hydroxydopamine lesioned nigrostriatal system of the adult rat
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DOI：
10.1016/0306-4522(95)00509-9
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发表时间：
1996-04-01
期刊：
影响因子：
3.3
通讯作者：
Dunnett, SB
中科院分区：
文献类型：
--
作者：
Brecknell, JE;Haque, NSK;Dunnett, SB
在试图重建6-羟基多巴胺损伤的黑质纹状体系统的成年大鼠，我们结合了胚胎腹侧中脑悬浮液的移植物的长斜“桥”移植物的成纤维细胞生长因子-4-转染RN-22神经鞘瘤细胞从神经元移植物的网站延伸到纹状体。在接受两种移植物后7周，处死动物并进行酪氨酸羟化酶的免疫组织化学处理。酪氨酸羟化酶免疫反应阳性轴突从黑质移植物延伸，沿着桥移植物延伸到纹状体，在纹状体可以看到终末分支。在一些实验动物的纹状体内注射逆行示踪剂Fluoro-gold，并被移植的神经元吸收，证实它们向纹状体的投射。与系统的解剖重建平行，在接受> 98%完全损伤的两种移植物的动物中证明了安非他明诱导的旋转减少。这种减少是最大的那些动物与最酪氨酸羟化酶免疫反应轴突在其桥移植。桥移植物的存在也导致神经元移植物存活率的增加，与那些接受神经元移植物但没有桥移植物的动物相比，在接受两种移植物的动物的移植物中发现了两倍的酪氨酸羟化酶免疫反应神经元。
In an attempt to reconstruct the 6-hydroxydopamine lesioned nigrostriatal system of the adult rat we have combined homotopic grafting of embryonic ventral mesencephalon suspensions with the implantation of long oblique ''bridge'' grafts of fibroblast growth factor-4-transfected RN-22 schwannoma cells stretching from the site of the neuronal grafts to the striatum. At seven weeks after receiving both grafts, animals were killed and processed for immunohistochemistry against tyrosine hydroxylase. Tyrosine hydroxylase-immunoreactive axons were seen to extend from the nigral grafts, along the bridge graft to the striatum where terminal arborizations could be seen. The retrograde tracer Fluoro-gold was injected intrastriatally in some of the experimental animals and was taken up by grafted neurons confirming their projection to the striatum. In parallel to the anatomical reconstruction of the system, a decrease in amphetamine-induced rotation was demonstrated in those animals receiving both grafts which had received > 98% complete lesions. This decrease was greatest in those animals with the most tyrosine hydroxylase-immunoreactive axons in their bridge grafts. The presence of the bridge graft also led to an increase in neuronal graft survival with twice as many tyrosine hydroxylase-immunoreactive neurons being found in the grafts of those animals that had received both grafts compared to those that had received a neuronal graft but no bridge graft.