Ascending sensory, but not other long-tract axons, regenerate into the connective tissue matrix that forms at the site of a spinal cord injury in mice
Ascending sensory, but not other long-tract axons, regenerate into the connective tissue matrix that forms at the site of a spinal cord injury in mice
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DOI：
10.1002/cne.10768
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发表时间：
2003-08-04
影响因子：
2.5
通讯作者：
Steward, O
中科院分区：
文献类型：
--
作者：
Inman, DM;Steward, O
小鼠在脊髓损伤后表现出独特的伤口愈合反应，其中病变部位填充了结缔组织基质。以前的研究表明，轴突生长到这个基质中，但轴突的来源仍然未知。目前的研究评估了这些轴突中是否有任何是长束再生的结果。C57BL/6小鼠接受挤压伤，存活6周至7个月。将生物素化葡聚糖胺(BDA)注射到躯体运动皮质以追踪皮质脊髓束(CST)的下行轴突，向中脑注射以标记包括红核脊髓束和网状脊髓束在内的脑干下行通路，或注入L5背根节以追踪一级感觉神经元的上行投射。用抗神经丝蛋白(NF)、5-羟色胺(5-HT)显示下行5-羟色胺能轴突的抗体、降钙素基因相关蛋白(CGRP)显示向上感觉轴突的抗体和硫酸软骨素蛋白多糖(CSPG)的抗体对其他小鼠的脊髓进行免疫细胞化学，以评估抑制轴突生长的分子的分布。核因子免疫染色显示病变部位的结缔组织基质中有轴突，证实了先前使用Protargol染色的研究。CST轴突没有进入结缔组织基质，但在邻近损伤部位的节段广泛萌发。红核脊髓束和网状脊髓束轴突也没有生长到病变部位。5-羟色胺阳性轴突延伸至病变边缘，少数轴突跟随星形胶质细胞突起进入病变边缘。与其他通路相比，BDA标记的上升感觉轴突确实延伸到结缔组织基质中并广泛分布于结缔组织基质中，尽管CGRP阳性的上升轴突亚群没有。这些结果表明，结缔组织基质允许某些类型的上升感觉轴突再生，但不允许其他轴突系统再生。(C)2003年Wiley-Liss，Inc.
Mice exhibit a unique wound healing response following spinal cord injury in which the lesion site fills in with a connective tissue matrix. Previous studies have revealed that axons grow into this matrix, but the source of the axons remained unknown. The present study assesses whether any of these axons were the result of long tract regeneration. C57Bl/6 mice received crush injuries and were allowed to survive for 6 weeks to 7 months. Biotinylated dextran amine (BDA) was injected into the somato-motor cortex to trace descending corticospinal tract (CST) axons, into the midbrain to label descending brainstem pathways including the rubrospinal and reticulospinal tracts, or into the L5 dorsal root ganglion to trace ascending projections of first-order sensory neurons. Spinal cords from other mice were prepared for immunocytochemistry using antibodies against neurofilament protein (NF), 5-HT to reveal descending serotonergic axons, calcitonin gene-related protein (CGRP) to reveal ascending sensory axons, and chondroitin sulfate proteoglycan (CSPG) to assess the distribution of molecules that are inhibitory to axon growth. NF immunostaining revealed axons in the connective tissue matrix at the lesion site, confirming previous studies that used protargol staining. CST axons did not enter the connective tissue matrix, but did sprout extensively in segments adjacent to the injury site. Rubrospinal and reticulospinal tract axons also did not grow into the lesion site. 5-HT-positive axons extended to the edge of the lesion, and a few axons followed astrocyte processes into the margins of the lesion site. In contrast to the other pathways, BDA-labeled ascending sensory axons did extend into and arborized extensively within the connective tissue matrix, although the subgroup of ascending axons that are positive for CGRP did not. These results indicate that the connective tissue matrix is permissive for regeneration of some classes of ascending sensory axons but not for other axonal systems. (C) 2003 Wiley-Liss, Inc.