AXONAL PROJECTIONS BETWEEN FETAL SPINAL-CORD TRANSPLANTS AND THE ADULT-RAT SPINAL-CORD - A NEUROANATOMICAL TRACING STUDY OF LOCAL INTERACTIONS
AXONAL PROJECTIONS BETWEEN FETAL SPINAL-CORD TRANSPLANTS AND THE ADULT-RAT SPINAL-CORD - A NEUROANATOMICAL TRACING STUDY OF LOCAL INTERACTIONS
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DOI：
10.1002/cne.903070211
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发表时间：
1991-05-08
影响因子：
2.5
通讯作者：
REIER, PJ
中科院分区：
文献类型：
--
作者：
JAKEMAN, LB;REIER, PJ
三种神经解剖学示踪剂已被用于绘制胚胎脊髓组织移植物与成年大鼠周围宿主脊髓之间形成的轴突投射。将胚胎第14天（E14）大鼠脊髓的固体块放入腰脊髓的半切抽吸腔中。注射（1）辣根过氧化物酶和麦胚凝集素结合辣根过氧化物酶的混合物，（2）荧光金，或（3）在移植后6周至14个月，将菜豆白细胞凝集素（PHA-L）植入移植物或宿主脊髓邻近节段，将顺行和逆行示踪剂注射到移植物中揭示了通常跨越移植物长度的广泛的内在投射。从移植物产生的轴突延伸到宿主脊髓中，距离宿主-移植物界面5 mm，最好通过用Fluoro-Gold逆行标记来显示。与这些观察结果相一致，PHA-L离子电渗注射到移植物中也在宿主脊髓中的可比距离处产生标记的轴突轮廓，并且在某些情况下，在宿主神经元周围观察到精心制作的终末场。然而，大多数PHA-L标记的传出纤维仅限于宿主-移植物边界附近，没有纤维穿过宿主和移植组织之间的细胞分区。例如，将Fluoro-Gold注射到移植物中导致脊髓和附近背根神经节内的宿主神经元的标记。在大多数情况下，脊髓灰质中的逆行标记神经元位于移植部位的0.5 mm内，尽管有些可以看到4-6 mm远。然而，根据HRP和Fluoro-Gold逆行标记的结果，宿主轴突向移植物内生长的距离和相对密度似乎是适度的。PHA-L顺行法进一步证实了这一点。而一些宿主纤维被认为是延伸到移植物，大多数的PHA-L含有轴突形成终端样的配置文件在或0.5毫米内的host-graft interface.The内在的连接和宿主移植物的预测在这些研究中获得的综合观点表明，胎儿脊髓组织的椎管内移植物可以建立一个短距离的intersegmented电路在受伤的，成人脊髓。这些观察结果与这样的观点一致，即这种移植物可能有助于损伤后脊髓分离节段之间形成功能中继。然而，事实上，大多数宿主和移植物衍生的轴突集中在宿主-移植物边界附近，引起了关于轴突生长和细胞相互作用的动力学的几个考虑。在这方面，本研究结果提供了一个有用的基线，阐明机制，调节轴突伸长在这个实验设置。这些结果也提供了一个框架，为未来的手术，药理学或分子操作，可能会提高宿主和移植组织之间的轴突相互作用的程度的测试。
Three neuroanatomical tracers have been employed to map the axonal projections formed between transplants of fetal spinal cord tissue and the surrounding host spinal cord in adult rats. Solid pieces of embryonic day 14 (E14) rat spinal cord were placed into hemisection aspiration cavities in the lumbar spinal cord. Injections of either (1) a mixture of horseradish peroxidase and wheat germ agglutinin- conjugated horseradish peroxidase, (2) Fluoro-Gold, or (3) Phaseolus vulgaris leucoagglutinin (PHA-L) were made into the transplants or the neighboring segments of the host spinal cord at 6 weeks to 14 months post-transplantation.Injections of anterograde and retrograde tracers into the transplants revealed extensive intrinsic projections that often spanned the length of the grafts. Axons arising from the transplants extended into the host spinal cord as far as 5 mm from the host-graft interface, as best revealed by retrograde labeling with Fluoro-Gold. Consistent with these observations, iontophoretic injections of PHA-L into the transplants also produced labeled axonal profiles at comparable distances in the host spinal cord, and in some instances elaborate terminals fields were observed surrounding host neurons. The majority of these efferent fibers labeled with PHA-L, however, were confined to the immediate vicinity of the host-graft boundary, and no fibers were seen traversing cellular partitions between host and transplant tissues.Host afferents to the transplants were also revealed by these tracing methods. For example, the injection of Fluoro-Gold into the grafts resulted in labeling of host neurons within the spinal cord and nearby dorsal root ganglia. In most cases, retrogradely labeled neurons in spinal gray matter were located within 0.5 mm of the graft site, although some were seen as far as 4-6 mm away. The distance and relative density of ingrowth exhibited by host axons into the grafts, however, appeared modest based upon the results of HRP and Fluoro-Gold retrograde labeling. This was further confirmed with the PHA-L anterograde method. Whereas some host fibers were seen extending into the transplants, the majority of PHA-L containing axons formed terminal-like profiles at or within 0.5 mm of the host-graft interface.The comprehensive view of intrinsic connectivity and host-graft projections obtained in these studies indicates that intraspinal grafts of fetal spinal cord tissue can establish a short-range intersegmental circuitry in the injured, adult spinal cord. These observations are consistent with the view that such grafts may contribute to the formation of a functional relay between separated segments of the spinal cord after injury. The fact, however, that the majority of host- and graft-derived axons were concentrated within the vicinity of the host-graft border raises several considerations about the dynamics of axonal growth and cellular interactions. In that regard, the present findings provide a useful baseline for elucidating mechanisms that regulate axonal elongation in this experimental setting. These results also provide a framework for future tests of surgical, pharmacological, or molecular manipulations that may enhance the degree of axonal interaction between host and graft tissues.