Strömberg I, Bygdeman M, Almqvist P
Department of Histology and Neurobiology, Karolinska Institute, Stockholm, Sweden.
J Comp Neurol. 1992 Jan 22;315(4):445-56. doi: 10.1002/cne.903150407.
Human fetal mesencephalic tissue was grafted to rats with unilateral lesions of the nigrostriatal pathway. The animals were immunosuppressed with cyclosporine A. Grafts were placed either into the lateral ventricle ipsilateral to the lesion or in the cingulate cortex above corpus callosum. The grafts and newly formed fibers were visualized by immunohistochemistry with antibodies against tyrosine hydroxylase (TH) and the human Thy-1 glycoprotein. TH-positive fibers covered the total volume of striatum when the graft was placed either in the ventricle or in the cortex. When the transplant was located in the ventricle, TH-positive cells migrated from the graft into host striatum. No cell migration was seen into any other areas than striatum. Cortex and septum were sparsely reinnervated by the graft, but not to a density higher than that normally seen. Globus pallidus was totally devoid of TH-positive fibers. When the graft was placed in cingulate cortex, fiber bundles penetrated through corpus callosum into either striatum, to arborize in its dorsal parts, or followed the medial side of the lateral ventricle to ventral limbic areas, where a fiber network also was formed. Human specific Thy-1-immunohistochemistry revealed positivity only on the lesioned side. These data suggest that dopamine neurons in human mesencephalic tissue, grafted to the rat brain, can migrate specifically into host striatum. Furthermore, TH-positive fiber outgrowth occurred only into dopamine denervated areas of the host, avoiding areas that are normally not innervated by nigral neurons, but also able to reach distant target cells.
将人胎儿中脑组织移植到黑质纹状体通路单侧损伤的大鼠体内。动物用环孢素A进行免疫抑制。移植物被置于损伤同侧的侧脑室或胼胝体上方的扣带回皮质。通过用抗酪氨酸羟化酶（TH）和人Thy-1糖蛋白的抗体进行免疫组织化学来观察移植物和新形成的纤维。当移植物置于脑室或皮质时，TH阳性纤维覆盖了纹状体的整个区域。当移植物位于脑室时，TH阳性细胞从移植物迁移到宿主纹状体。除纹状体外，未见细胞迁移到任何其他区域。皮质和隔区被移植物稀疏地重新支配，但密度未高于正常所见。苍白球完全没有TH阳性纤维。当移植物置于扣带回皮质时，纤维束穿过胼胝体进入纹状体，在其背侧分支，或沿着侧脑室内侧到达腹侧边缘区域，在那里也形成了纤维网络。人特异性Thy-1免疫组织化学显示仅在损伤侧呈阳性。这些数据表明，移植到大鼠脑内的人胎儿中脑组织中的多巴胺神经元可以特异性地迁移到宿主纹状体中。此外，TH阳性纤维只向宿主的多巴胺去神经支配区域生长，避开正常情况下黑质神经元不支配的区域，但也能够到达远处的靶细胞。
