Wang X, Messing A, David S
Centre for Research in Neuroscience, The Montreal General Hospital Research Institute and McGill University, 1650 Cedar Avenue, Montreal, Quebec, H3G 1A4, Canada.
Exp Neurol. 1997 Dec;148(2):568-76. doi: 10.1006/exnr.1997.6702.
We have examined the regeneration of corticospinal tract fibers and expression of various extracellular matrix (ECM) molecules and intermediate filaments [vimentin and glial fibrillary acidic protein (GFAP)] after dorsal hemisection of the spinal cord of adult GFAP-null and wild-type littermate control mice. The expression of these molecules was also examined in the uninjured spinal cord. There was no increase in axon sprouting or long distance regeneration in GFAP-/- mice compared to the wild type. In the uninjured spinal cord (i) GFAP was expressed in the wild type but not the mutant mice, while vimentin was expressed in astrocytes in the white matter of both types of mice; (ii) laminin and fibronectin immunoreactivity was localized to blood vessels and meninges; (iii) tenascin and chondroitin sulfate proteoglycan (CSPG) labeling was detected in astrocytes and the nodes of Ranvier in the white matter; and (iv) in addition, CSPG labeling which was generally less intense in the gray matter of mutant mice. Ten days after hemisection there was a large increase in vimentin+ cells at the lesion site in both groups of mice. These include astrocytes as well as meningeal cells that migrate into the wound. The center of these lesions was filled by laminin+/fibronectin+ cells. Discrete strands of tenascin-like immunoreactivity were seen in the core of the lesion and lining its walls. Marked increases in CSPG labeling was observed in the CNS parenchyma on either side of the lesion. These results indicate that the absence of GFAP in reactive astrocytes does not alter axonal sprouting or regeneration. In addition, except for CSPG, the expression of various ECM molecules appears unaltered in GFAP-/- mice.
我们研究了成年GFAP基因敲除小鼠和野生型同窝对照小鼠脊髓背侧半横断后皮质脊髓束纤维的再生情况，以及各种细胞外基质（ECM）分子和中间丝[波形蛋白和胶质纤维酸性蛋白（GFAP）]的表达。还在未损伤的脊髓中检测了这些分子的表达。与野生型相比，GFAP基因敲除小鼠的轴突发芽或长距离再生没有增加。在未损伤的脊髓中：（i）野生型小鼠表达GFAP，而突变型小鼠不表达，波形蛋白在两种小鼠白质的星形胶质细胞中均有表达；（ii）层粘连蛋白和纤连蛋白免疫反应定位于血管和脑膜；（iii）在白质的星形胶质细胞和郎飞结处检测到腱生蛋白和硫酸软骨素蛋白聚糖（CSPG）标记；（iv）此外，突变型小鼠灰质中的CSPG标记通常较弱。半横断后10天，两组小鼠损伤部位波形蛋白阳性细胞大量增加。这些细胞包括星形胶质细胞以及迁移到伤口的脑膜细胞。这些损伤的中心充满了层粘连蛋白阳性/纤连蛋白阳性细胞。在损伤核心及其壁层可见离散的腱生蛋白样免疫反应条带。在损伤两侧的中枢神经系统实质中观察到CSPG标记显著增加。这些结果表明，反应性星形胶质细胞中GFAP的缺失不会改变轴突发芽或再生。此外，除CSPG外，GFAP基因敲除小鼠中各种ECM分子的表达似乎未改变。
