Growth-modulating molecules are associated with invading Schwann cells and not astrocytes in human traumatic spinal cord injury
Growth-modulating molecules are associated with invading Schwann cells and not astrocytes in human traumatic spinal cord injury
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DOI：
10.1093/brain/awl374
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发表时间：
2007-04-01
期刊：
影响因子：
14.5
通讯作者：
Brook, Gary A.
中科院分区：
文献类型：
--
作者：
Buss, Armin;Pech, Katrin;Brook, Gary A.
尽管近年来取得了相当大的进展，但脊髓损伤（SCI）后轴突再生失败的潜在机制仍然只有部分了解。实验数据表明，切断轴突生长的主要障碍是最终支配病变部位的瘢痕组织，在严重损伤中，瘢痕组织由结缔组织和充满液体的囊肿组成，周围有致密的星形胶质细胞瘢痕。反应性星形胶质细胞和浸润细胞，如成纤维细胞，产生致密的细胞外基质（ECM），代表轴突再生的物理和分子屏障。在人类情况下，创伤性SCI后形成的瘢痕组织的分子组成的相关数据很少。因此，对假定的生长抑制和生长促进分子的表达进行了详细的研究，在死后的人脊髓样本中，取自严重创伤性SCI后死亡的患者。病变诱导的瘢痕可细分为雪旺细胞占主导地位的领域，其中包含大的神经瘤和周围致密的ECM，以及轮廓分明的星形胶质细胞瘢痕，其将雪旺细胞/ECM丰富的区域与完整的脊髓实质分离。轴突生长调节分子胶原IV，层粘连蛋白和纤维连接蛋白都存在于创伤后瘢痕组织。这些分子几乎只存在于雪旺氏细胞丰富的结构域，对PNS轴突具有明显的生长促进作用。在星形胶质细胞结构域中，这些分子被限制在血管壁中，而没有与位于该区域的少数再生CNS神经突共定位。两者合计，这些结果支持的概念，它是星形胶质细胞室，发挥了主导作用，防止中枢神经系统轴突再生。未能证明任何与星形胶质细胞瘢痕相关的IV型胶原蛋白、层粘连蛋白或纤连蛋白上调，表明其他分子可能在预防人类SCI后轴突再生中发挥更重要的作用。
Despite considerable progress in recent years, the underlying mechanisms responsible for the failure of axonal regeneration after spinal cord injury (SCI) remain only partially understood. Experimental data have demonstrated that a major impediment to the outgrowth of severed axons is the scar tissue that finally dominates the lesion site and, in severe injuries, is comprised of connective tissue and fluid-filled cysts, surrounded by a dense astroglial scar. Reactive astrocytes and infiltrating cells, such as fibroblasts, produce a dense extracellular matrix (ECM) that represents a physical and molecular barrier to axon regeneration. In the human situation, correlative data on the molecular composition of the scar tissue that forms following traumatic SCI is scarce. A detailed investigation on the expression of putative growth-inhibitory and growth-promoting molecules was therefore performed in samples of post-mortem human spinal cord, taken from patients who died following severe traumatic SCI. The lesion-induced scar could be subdivided into a Schwann cell dominated domain which contained large neuromas and a surrounding dense ECM, and a well delineated astroglial scar that isolated the Schwann cell/ECM rich territories from the intact spinal parenchyma. The axon growth-modulating molecules collagen IV, laminin and fibronectin were all present in the post-traumatic scar tissue. These molecules were almost exclusively found in the Schwann cell-rich domain which had an apparent growth-promoting effect on PNS axons. In the astrocytic domain, these molecules were restricted to blood vessel walls without a co-localization with the few regenerating CNS neurites located in this region. Taken together, these results favour the notion that it is the astroglial compartment that plays a dominant role in preventing CNS axon regeneration. The failure to demonstrate any collagen IV, laminin or fibronectin upregulation associated with the astroglial scar suggests that other molecules may play a more significant role in preventing axon regeneration following human SCI.