Gilmore S A, Sims T J
Department of Anatomy University of Arkansas for Medical Sciences Little Rock 72205, USA.
J Anat. 1997 Jan;190 ( Pt 1)(Pt 1):5-21. doi: 10.1046/j.1469-7580.1997.19010005.x.
This review summarises some of the major findings derived from studies using the model of a glia-depleted environment developed and characterised in this laboratory. Glial depletion is achieved by exposure of the immature rodent spinal cord to x-radiation which markedly reduces both astrocyte and oligodendrocyte populations and severely impairs myelination. This glia-depleted, hypomyelinated state presents a unique opportunity to examine aspects of spinal cord maturation in the absence of a normal glial population. An associated sequela within 2-3 wk following irradiation is the appearance of Schwann cells in the dorsal portion of the spinal cord. Characteristics of these intraspinal Schwann cells, their patterns of myelination or ensheathment, and their interrelations with the few remaining central glia have been examined. A later sequela is the development of Schwann cells in the ventral aspect of the spinal cord where they occur predominantly in the grey matter. Characteristics of these ventrally situated intraspinal Schwann cells are compared with those of Schwann cells located dorsally. Recently, injury responses have been defined in the glia-depleted spinal cord subsequent to the lesioning of dorsal spinal nerve roots. In otherwise normal animals, dorsal nerve root injury induces an astrocytic reaction within the spinal segments with which the root(s) is/are associated. Lesioning of the 4th lumbar dorsal root on the right side in irradiated or nonirradiated animals results in markedly different glial responses with little astrocytic scarring in the irradiated animals. Tracing studies reveal that these lesioned dorsal root axons regrow rather robustly into the spinal cord in irradiated but not in nonirradiated animals. To examine role(s) of glial cells in preventing this axonal regrowth, glial cells are now being added back to this glia-depleted environment through transplantation of cultured glia into the irradiated area. Transplanted astrocytes establish barrier-like arrangements within the irradiated cords and prevent axonal regrowth into the cord. Studies using other types of glial cultures (oligodendrocyte or mixed) are ongoing.
本综述总结了一些主要研究发现，这些发现源自使用本实验室开发并表征的胶质细胞耗竭环境模型所开展的研究。通过将未成熟啮齿动物的脊髓暴露于X射线来实现胶质细胞耗竭，这会显著减少星形胶质细胞和少突胶质细胞的数量，并严重损害髓鞘形成。这种胶质细胞耗竭、髓鞘形成不足的状态为在缺乏正常胶质细胞群体的情况下研究脊髓成熟的各个方面提供了独特的机会。照射后2 - 3周内出现的一个相关后遗症是脊髓背侧出现雪旺细胞。已对这些脊髓内雪旺细胞的特征、它们的髓鞘形成或包裹模式以及它们与少数剩余中枢胶质细胞的相互关系进行了研究。一个较晚出现的后遗症是脊髓腹侧雪旺细胞的发育，它们主要出现在灰质中。将这些位于腹侧的脊髓内雪旺细胞的特征与位于背侧的雪旺细胞的特征进行了比较。最近，在背侧脊髓神经根损伤后，已确定了胶质细胞耗竭的脊髓中的损伤反应。在其他方面正常的动物中，背根神经损伤会在与之相关的脊髓节段内引发星形胶质细胞反应。在受照射或未受照射的动物中，右侧第4腰段背根损伤会导致明显不同的胶质细胞反应，受照射动物中几乎没有星形胶质细胞瘢痕形成。追踪研究表明，在受照射的动物中，这些受损的背根轴突能相当强劲地向脊髓内再生，而在未受照射的动物中则不能。为了研究胶质细胞在阻止这种轴突再生中的作用，目前正通过将培养的胶质细胞移植到受照射区域，将胶质细胞重新添加到这种胶质细胞耗竭的环境中。移植的星形胶质细胞在受照射的脊髓内形成类似屏障的结构，阻止轴突向脊髓内再生。使用其他类型胶质细胞培养物（少突胶质细胞或混合培养物）的研究正在进行中。
