Cloutier Frank, Sears-Kraxberger Ilse, Keachie Krista, Keirstead Hans S
Reeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, School of Medicine, University of California at Irvine, 845 Health Sciences Road, Irvine, CA 92697, USA ; Département de Biologie de l'Université de Moncton, 18 Antonine-Maillet, Moncton, NB, Canada E1A 3E9.
Clin Dev Immunol. 2013;2013:812456. doi: 10.1155/2013/812456. Epub 2013 Nov 11.
The glial scar formed by reactive astrocytes and axon growth inhibitors associated with myelin play important roles in the failure of axonal regeneration following central nervous system (CNS) injury. Our laboratory has previously demonstrated that immunological demyelination of the CNS facilitates regeneration of severed axons following spinal cord injury. In the present study, we evaluate whether immunological demyelination is accompanied with astrogliosis. We compared the astrogliosis and macrophage/microglial cell responses 7 days after either immunological demyelination or a stab injury to the dorsal funiculus. Both lesions induced a strong activated macrophage/microglial cells response which was significantly higher within regions of immunological demyelination. However, immunological demyelination regions were not accompanied by astrogliosis compared to stab injury that induced astrogliosis which extended several millimeters above and below the lesions, evidenced by astroglial hypertrophy, formation of a glial scar, and upregulation of intermediate filaments glial fibrillary acidic protein (GFAP). Moreover, a stab or a hemisection lesion directly within immunological demyelination regions did not induced astrogliosis within the immunological demyelination region. These results suggest that immunological demyelination creates a unique environment in which astrocytes do not form a glial scar and provides a unique model to understand the putative interaction between astrocytes and activated macrophage/microglial cells.
由反应性星形胶质细胞和与髓磷脂相关的轴突生长抑制剂形成的胶质瘢痕，在中枢神经系统（CNS）损伤后轴突再生失败中起重要作用。我们实验室先前已证明，中枢神经系统的免疫性脱髓鞘促进脊髓损伤后切断轴突的再生。在本研究中，我们评估免疫性脱髓鞘是否伴有星形胶质细胞增生。我们比较了免疫性脱髓鞘或背侧索刺伤7天后的星形胶质细胞增生以及巨噬细胞/小胶质细胞反应。两种损伤均诱导了强烈的活化巨噬细胞/小胶质细胞反应，在免疫性脱髓鞘区域内该反应明显更高。然而，与刺伤相比，免疫性脱髓鞘区域未伴有星形胶质细胞增生，刺伤诱导的星形胶质细胞增生在损伤部位上方和下方数毫米处延伸，表现为星形胶质细胞肥大、胶质瘢痕形成以及中间丝胶质纤维酸性蛋白（GFAP）上调。此外，直接在免疫性脱髓鞘区域内的刺伤或半切损伤并未在免疫性脱髓鞘区域诱导星形胶质细胞增生。这些结果表明，免疫性脱髓鞘创造了一种独特的环境，其中星形胶质细胞不会形成胶质瘢痕，并提供了一个独特的模型来理解星形胶质细胞与活化的巨噬细胞/小胶质细胞之间的假定相互作用。
