Itoh Y, Sugawara T, Kowada M, Tessler A
Department of Neurosurgery, Akita University School of Medicine, Japan.
J Comp Neurol. 1992 Sep 8;323(2):198-208. doi: 10.1002/cne.903230205.
Cut dorsal root axons regenerate into intraspinal transplants of fetal spinal cord and establish synaptic connections there. The aims of the present study were to describe the progression of dorsal root growth within the transplants and the maturation of transplant morphology and to determine whether the regenerated dorsal root axons persist within the transplants or eventually withdraw. Embryonic (E) day 14 spinal cord was grafted into the lumbar enlargement of adult Sprague-Dawley rats, and the L4 or L5 dorsal root was cut and juxtaposed to the transplants. The morphology of the transplants was examined from 1 day to over 1 year after surgery, and the regenerated dorsal roots were labeled with immunohistochemical methods to study the subset that contains calcitonin gene-related peptide (CGRP). Embryonic spinal cord transplants survived and grew within the host spinal cord in over 90% of the animals. Transplant volume increased and the morphology of the transplants matured over the first 12 weeks and then did not change for 48-60 weeks. During the first week the transplants were composed of dissociated neurons, glia, and hematogenous cells with considerable extracellular space between them. Subsequently, the grafted neurons became densely aggregated, and non-neuronal elements such as inflammatory cells and myelin debris disappeared. CGRP-immunoreactive dorsal roots began to regenerate into the transplants within 24 hours, formed dense bundles by 4 days, and were still present at 60 weeks, the longest survival period examined. Myelination of axons within transplants began at 2 weeks. Quantitative analysis showed that the area of the transplants occupied by CGRP-labeled axons and the distribution area of the labeled axons within the transplants increased until 12 weeks and persisted unchanged for over 48 weeks. These results indicate that regenerated dorsal root axons are permanently maintained within transplants of embryonic spinal cord and suggest that the transplants can contribute to the permanent restoration of damaged intraspinal neural circuits.
切断的背根轴突可长入胎儿脊髓的脊髓内移植体并在那里建立突触连接。本研究的目的是描述移植体内背根生长的进程以及移植体形态的成熟过程，并确定再生的背根轴突是否在移植体内持续存在或最终退缩。将胚胎（E）第14天的脊髓移植到成年Sprague-Dawley大鼠的腰膨大处，切断L4或L5背根并使其与移植体相邻。在手术后1天至1年多的时间内检查移植体的形态，并用免疫组织化学方法标记再生的背根，以研究含有降钙素基因相关肽（CGRP）的子集。超过90%的动物胚胎脊髓移植体在宿主脊髓内存活并生长。移植体体积在前12周增加，其形态成熟，然后在48 - 60周内没有变化。在第一周，移植体由离散的神经元、神经胶质细胞和造血细胞组成，它们之间有相当大的细胞外间隙。随后，移植的神经元紧密聚集，炎症细胞和髓磷脂碎片等非神经元成分消失。CGRP免疫反应性背根在24小时内开始长入移植体，4天时形成密集束，在60周（检查的最长存活期）时仍然存在。移植体内轴突的髓鞘形成在2周时开始。定量分析表明，CGRP标记的轴突所占移植体的面积以及标记轴突在移植体内的分布面积在前12周增加，并在超过48周内保持不变。这些结果表明，再生的背根轴突在胚胎脊髓移植体内永久维持，并提示移植体可有助于受损脊髓内神经回路的永久修复。
