Itoh Y, Tessler A
Philadelphia VA Hospital, Pennsylvania.
J Comp Neurol. 1990 Dec 8;302(2):272-93. doi: 10.1002/cne.903020207.
Cut dorsal root axons regenerate into transplants of embryonic spinal cord and form synapses that resemble those found in the dorsal horn of normal spinal cord. One aim of the present study was to determine whether these axons also regenerate into and establish synapses within transplants of embryonic brain. A second aim was to compare the patterns of growth in embryonic brain and spinal cord transplants. Embryonic spinal cord or brain was transplanted into the lumbar enlargement of adult Sprague-Dawley rats, the L4 or L5 dorsal root was cut, and the cut root was juxtaposed to the transplant. The transplants included whole pieces or dissociated cell suspensions of embryonic day 14 (E14) spinal cord, or whole pieces of E14 neocortex, E18 occipital cortex, E15 cerebellum, or E18 hippocampus. One month later the regenerated dorsal root axons were labeled by immunocytochemical methods to demonstrate calcitonin gene-related peptide (CGRP). CGRP-immunoreactive axons regenerated into all the transplants examined and formed synapses in the neocortex and cerebellum transplants in which they were sought. Synapses were far rarer in neocortex and cerebellum than we had observed previously in transplanted spinal cord, and the patterns of growth differed in transplants of spinal cord and brain. In solid transplants of spinal cord, regenerated axons remained relatively close to the interface with the dorsal root, branched, and formed bundles. Areas of dense ingrowth were separated by regions with few labeled axons. In transplants of brain regions, the regenerated axons were few, unbranched, and appeared as individual fibers rather than in bundles, but they were distributed widely in neocortex transplants. The results of quantitative studies confirmed these observations. The area fraction occupied by regenerated axons in solid spinal cord transplants was significantly larger than in occipital cortex or cerebellum transplants. Distribution histograms of the area occupied in transplants demonstrated that regenerated axons were distributed sparsely but homogeneously in transplants of brain, whereas spinal cord transplants were heterogeneous for regenerated axons and contained areas in which growth was dense or sparse. In contrast, several measurements of axon distribution, including area, longest axis, and length of lateral extension, indicated that CGRP-labeled axons spread more widely in occipital cortex transplants than in solid transplants of spinal cord or cerebellum. The results indicate that embryonic CNS tissues that are not normal targets support or enhance the growth of severed dorsal roots and suggest that the conditions that constitute a permissive environment for regenerating axons are relatively nonspecific.(ABSTRACT TRUNCATED AT 400 WORDS)
切断的背根轴突能再生进入胚胎脊髓移植体并形成类似于正常脊髓背角中发现的突触。本研究的一个目的是确定这些轴突是否也能再生进入胚胎脑移植体并在其中建立突触。第二个目的是比较胚胎脑和脊髓移植体中的生长模式。将胚胎脊髓或脑移植到成年Sprague-Dawley大鼠的腰膨大处，切断L4或L5背根，并将切断的神经根与移植体并列。移植体包括胚胎第14天（E14）脊髓的整块组织或解离的细胞悬液，或E14新皮层、E18枕叶皮层、E15小脑或E18海马体的整块组织。一个月后，通过免疫细胞化学方法标记再生的背根轴突以显示降钙素基因相关肽（CGRP）。CGRP免疫反应性轴突再生进入所有检查的移植体，并在新皮层和小脑移植体中形成突触，在这些移植体中对其进行了观察。新皮层和小脑中的突触比我们之前在移植脊髓中观察到的要稀少得多，并且脊髓和脑移植体中的生长模式也不同。在脊髓的实体移植体中，再生轴突相对靠近与背根的界面，分支并形成束。密集生长区域被标记轴突少的区域隔开。在脑区移植体中，再生轴突很少，无分支，呈单根纤维而非束状出现，但它们广泛分布在新皮层移植体中。定量研究结果证实了这些观察结果。实体脊髓移植体中再生轴突所占的面积分数显著大于枕叶皮层或小脑移植体。移植体中所占面积的分布直方图表明，再生轴突在脑移植体中分布稀疏但均匀，而脊髓移植体中再生轴突不均匀，包含生长密集或稀疏的区域。相比之下，包括面积、最长轴和侧向延伸长度在内的几种轴突分布测量表明，CGRP标记的轴突在枕叶皮层移植体中的扩散比在脊髓或小脑的实体移植体中更广泛。结果表明，并非正常靶标的胚胎中枢神经系统组织支持或促进切断的背根生长，并表明构成轴突再生允许环境的条件相对非特异性。（摘要截短至400字）
