Immunological demyelination triggers macrophage/microglial cells activation without inducing astrogliosis.

Immunological demyelination triggers macrophage/microglial cells activation without inducing astrogliosis.
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DOI:
10.1155/2013/812456
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发表时间:
2013
影响因子:
--
通讯作者:
Keirstead HS
Keirstead HS
中科院分区:
其他
文献类型:
--
作者:
Cloutier F;Sears-Kraxberger I;Keachie K;Keirstead HS

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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神经胶质疤痕在中枢神经系统(CNS)损伤后轴突再生失败中发挥重要作用。我们的实验室之前已经证明,中枢神经系统的免疫性脱髓鞘有助于脊髓损伤后切断的轴突的再生。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索刺伤后 7 天的星形胶质细胞增生和巨噬细胞/小胶质细胞反应。两种病变均诱导强烈活化的巨噬细胞/小胶质细胞反应,该反应在免疫性脱髓鞘区域内显着较高。然而,与刺伤诱导星形胶质细胞增生(在病变上下延伸数毫米)相比,免疫性脱髓鞘区域并不伴有星形胶质细胞增生,表现为星形胶质细胞肥大、胶质疤痕形成和中间丝胶质纤维酸性蛋白(GFAP)的上调。此外,直接在免疫脱髓鞘区域内的刺伤或半切损伤不会诱导免疫脱髓鞘区域内的星形胶质细胞增生。这些结果表明,免疫脱髓鞘创造了一个独特的环境,在该环境中星形胶质细胞不会形成神经胶质疤痕,并提供了一个独特的模型来理解星形胶质细胞和活化的巨噬细胞/小胶质细胞之间的假定相互作用。
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.
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