Friehs G M, Parker R G, He L S, Haines S J, Turner D A, Ebner T J
Department of Neurosurgery, University of Minnesota, Minneapolis 55455.
J Neural Transplant Plast. 1991;2(2):141-56. doi: 10.1155/NP.1991.141.
In the rat several paradigms of grafting of adrenal medulla into the striatum were studied following the induction of a parkinsonian model, using a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra. Direct autologous grafting of adrenal medulla into the caudate-putamen complex, a radiofrequency lesion of the striatum alone, and a radiofrequency lesion followed by delayed grafting of adrenal medulla were compared by analyzing rotational behavior. Direct grafting of adrenal medulla produced an overall reduction in apomorphine induced turning behavior by 43.5% when compared with controls. Radiofrequency lesioning of the striatum without graft showed the best improvement over control animals with a 92% reduction in the total number of rotations induced by apomorphine. Delayed grafting into the caudate lesion cavity also produced a dramatic reduction in motor asymmetry but did not improve the behavioral outcome over that of the lesion alone. Animals receiving only radiofrequency lesions exhibited a band of increased tyrosine hydroxylase like immunoreactivity bordering the lesion cavity. Graft survival was limited in the non-lesioned animals but appeared enhanced in the animals whose striatum was previously lesioned. Lesion location within the striatum influenced the behavioral outcome. Large reductions in apomorphine-induced rotations could result from small lesions of the dorso-lateral striatum. These findings indicate that selective destruction of the caudate-putamen complex without tissue transplantation produces a dramatic reduction in the motor asymmetry of 6-OHDA treated rats. Suggested explanations for the decrease in induced rotational behavior with radiofrequency lesions include a decrease in the number of striatal dopamine receptors following cell destruction and lesion-induced recovery of host dopaminergic afferents. Striatal damage in critical areas can reverse some of the motor behavior associated with the 6-OHDA model and needs to be considered when evaluating the effects of neural grafting in this model.
在大鼠中，通过单侧黑质6-羟基多巴胺（6-OHDA）损伤诱导帕金森模型后，研究了几种将肾上腺髓质移植到纹状体的范例。通过分析旋转行为，比较了将肾上腺髓质直接自体移植到尾状核-壳核复合体、单独进行纹状体的射频损伤以及射频损伤后延迟移植肾上腺髓质的效果。与对照组相比，直接移植肾上腺髓质使阿扑吗啡诱导的旋转行为总体减少了43.5%。未移植的纹状体射频损伤显示出比对照动物更好的改善，阿扑吗啡诱导的总旋转次数减少了92%。延迟移植到尾状核损伤腔也使运动不对称性显著降低，但与仅损伤相比，行为结果并未得到改善。仅接受射频损伤的动物在损伤腔边缘出现一条酪氨酸羟化酶样免疫反应性增加带。在未损伤的动物中移植存活率有限，但在纹状体先前已损伤的动物中似乎有所提高。纹状体内的损伤位置影响行为结果。背外侧纹状体的小损伤可导致阿扑吗啡诱导的旋转大幅减少。这些发现表明，在不进行组织移植的情况下选择性破坏尾状核-壳核复合体可使6-OHDA处理的大鼠运动不对称性显著降低。射频损伤导致诱导旋转行为减少的推测解释包括细胞破坏后纹状体多巴胺受体数量减少以及损伤诱导的宿主多巴胺能传入纤维恢复。关键区域的纹状体损伤可逆转与6-OHDA模型相关的一些运动行为，在评估该模型中神经移植的效果时需要考虑这一点。
