Abrous N, Guy J, Vigny A, Calas A, Le Moal M, Herman J P
INSERM U-259, Université de Bordeaux II, France.
J Comp Neurol. 1988 Jul 1;273(1):26-41. doi: 10.1002/cne.902730104.
The aim of the study was to obtain a description of some aspects of the development of intracerebral dopaminergic grafts, namely, the time course of the glial reaction and its relation to cell division on one hand, and the development of graft-originated innervation and its dependence on adequate matching of the implanted neurons and target site on the other hand. Cell suspensions obtained from the mesencephalon or hypothalamus of embryonic day (ED) 14 rat embryos were implanted into the striatum or lateral hypothalamus of adult rats following the destruction of the nigrostriatal system of the hosts. Animals were sacrificed at different postimplantation times, and the development of the graft was followed by immunohistochemistry by using antisera directed against tyrosine hydroxylase (TH) or glial fibrillary acidic protein (GFA). Furthermore, the existence of cell division at various times following implantation was examined by performing autoradiography on immunostained sections after prior intraventricular administration of 3H-thymidine to the host. The first stage of the development of intracerebral grafts was characterized by the existence of intense cell division within the grafted tissue, lasting about 2 weeks, and also in the host tissue surrounding the graft, lasting only about 6 days. The cell division in the host tissue was paralleled by the existence of a strong glial reaction which, however, did not extend into the graft itself. Glial reaction in the host tissue gradually decreased at later times and disappeared by 4 weeks postimplantation without leaving behind a noticeable glial scar. The graft itself was, however, transiently filled with a population of reactive astroglial cells between 3 and 6 weeks postimplantation. Within grafts of mesencephalic tissue located in the striatum TH-positive neurons were distributed evenly at short times postimplantation (2-6 days). At later time a compartmentation could be observed, with TH-positive neurons being aligned along the graft-host interface or clustered within the graft itself. Innervation of the host tissue by TH-positive fibers increased between 1 and 6 weeks postimplantation. On the other hand, no compartmentation and reinnervation of surrounding host tissue was observed for intrahypothalamic grafts of mesencephalic tissue or intrastriatal grafts of hypothalamic tissue. This last observation indicates that adequate matching of implanted neurons and target tissue plays an important role in the development of intracerebral dopaminergic grafts.
本研究的目的是描述脑内多巴胺能移植体发育的某些方面，一方面是胶质反应的时间进程及其与细胞分裂的关系，另一方面是移植体起源的神经支配的发育及其对植入神经元与靶位点适当匹配的依赖性。从胚胎第14天（ED14）大鼠胚胎的中脑或下丘脑获得的细胞悬液，在破坏宿主的黑质纹状体系统后，植入成年大鼠的纹状体或下丘脑外侧。在植入后的不同时间处死动物，并通过使用针对酪氨酸羟化酶（TH）或胶质纤维酸性蛋白（GFA）的抗血清进行免疫组织化学来追踪移植体的发育。此外，在向宿主脑室内预先注射3H-胸腺嘧啶后，通过对免疫染色切片进行放射自显影来检查植入后不同时间的细胞分裂情况。脑内移植体发育的第一阶段的特征是，移植组织内存在强烈的细胞分裂，持续约2周，宿主组织中围绕移植体的细胞分裂仅持续约6天。宿主组织中的细胞分裂伴随着强烈的胶质反应，然而，这种反应并未延伸到移植体本身。宿主组织中的胶质反应在后期逐渐减弱，在植入后4周消失，没有留下明显的胶质瘢痕。然而，在植入后3至6周期间，移植体本身短暂地充满了一群反应性星形胶质细胞。位于纹状体内的中脑组织移植体中，TH阳性神经元在植入后短时间内（2 - 6天）均匀分布。在后期，可以观察到一种分隔现象，TH阳性神经元沿着移植体 - 宿主界面排列或聚集在移植体内部。TH阳性纤维对宿主组织的神经支配在植入后1至6周增加。另一方面，对于中脑组织的下丘脑内移植体或下丘脑组织的纹状体内移植体，未观察到周围宿主组织的分隔和再支配现象。最后这一观察结果表明，植入神经元与靶组织的适当匹配在脑内多巴胺能移植体的发育中起重要作用。
