Cheng C, Zochodne D W
Department of Clinical Neurosciences and the Neuroscience Research Group, Room 182A, University of Calgary, 3330 Hospital Drive N.W., Calgary, AB, Canada T2N 4N1.
Neuroscience. 2002;115(1):321-9. doi: 10.1016/s0306-4522(02)00291-9.
Following injury to a peripheral nerve, changes in the behavior of Schwann cells help to define the subsequent microenvironment for regeneration. Such changes, however, have almost exclusively been considered in the context of Wallerian degeneration distal to an injury, where loss of axonal contact or input is thought to be critical to the changes that occur. This supposition, however, may be incorrect in the proximal stumps where axons are still in contact with their cell bodies. In this work, we studied aspects of in vivo Schwann cell behavior after injury within the microenvironment of proximal stumps of transected rat sciatic nerves, where axons are preserved. In particular we studied this microenvironment proximal to the outgrowth zone, in an area containing intact myelinated fibers and a perineurial layer, by using double immunolabelling of Schwann cell markers and 5-bromo-2'-deoxyuridine (BrdU) labeling of proliferating cells. In normal sciatic nerve, Schwann cells were differentiated, in an orderly fashion, into those associated with unmyelinated fibers that labeled with glial fibrillary acidic protein (GFAP) and those associated with myelinated fibers that could be identified by individual axons and myelin sheaths. After sciatic nerve transection, there was rapid and early expansion in the population of GFAP-labeled cells in proximal stumps that was generated in part, by de novo expression of GFAP in Schwann cells of myelinated fibers. Schwann cells from this population also underwent proliferation, indicated by progressive rises in BrdU and GFAP double labeling. Finally, this Schwann cell pool also developed the property of migration, traveling to the distal outgrowth zone, but also with lateral penetration into the perineurium and epineurium, while in intimate contact with new axons. The findings suggest that other signals, in the injured proximal nerve stumps, beyond actual loss of axons, induce 'mature' Schwann cells of myelinated axons to dedifferentiate into those that up-regulated their GFAP expression, proliferate and migrate with axons.
外周神经损伤后，施万细胞行为的变化有助于确定后续的再生微环境。然而，此类变化几乎完全是在损伤远端的沃勒变性背景下被考虑的，在那里轴突接触或输入的丧失被认为是所发生变化的关键因素。然而，这种假设在近端残端可能是不正确的，因为近端残端的轴突仍与它们的细胞体相连。在这项研究中，我们研究了切断的大鼠坐骨神经近端残端微环境中损伤后体内施万细胞行为的各个方面，其中轴突得以保留。特别地，我们通过对施万细胞标志物进行双重免疫标记以及对增殖细胞进行5-溴-2'-脱氧尿苷（BrdU）标记，研究了生长区近端的这个微环境，该区域包含完整的有髓纤维和神经束膜层。在正常坐骨神经中，施万细胞以有序的方式分化为与用胶质纤维酸性蛋白（GFAP）标记的无髓纤维相关的细胞以及与可通过单个轴突和髓鞘识别的有髓纤维相关的细胞。坐骨神经切断后，近端残端中GFAP标记细胞群体迅速且早期扩张，部分原因是有髓纤维的施万细胞中GFAP的从头表达。来自这个群体的施万细胞也经历了增殖，BrdU和GFAP双重标记的逐渐增加表明了这一点。最后，这个施万细胞池还发展出迁移特性，迁移到远端生长区，同时也横向渗透到神经束膜和神经外膜，并且与新轴突紧密接触。这些发现表明，在受损的近端神经残端中，除了轴突的实际丧失之外，其他信号会诱导有髓轴突的“成熟”施万细胞去分化为那些上调其GFAP表达、增殖并与轴突一起迁移的细胞。
