The Effect of Stereotactic Injections on Demyelination and Remyelination: a Study in the Cuprizone Model
The Effect of Stereotactic Injections on Demyelination and Remyelination: a Study in the Cuprizone Model
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DOI：
10.1007/s12031-017-0888-y
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发表时间：
2017-04-01
影响因子：
3.1
通讯作者：
Stangel, Martin
中科院分区：
文献类型：
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作者：
Tejedor, Laura Salinas;Wostradowski, Tanja;Stangel, Martin
髓鞘再生是多发性硬化症等中枢神经系统脱髓鞘性疾病的自然修复机制。一些动物模型已经被用来研究脱髓鞘和再脱髓鞘。在毒性动物模型中，口服铜酮毒素可导致白质和灰质脱髓鞘。相反，局灶性脱髓鞘模型包括立体定向应用毒素，如溶卵磷脂或溴化乙锭。注射过程产生局部血脑屏障（BBB）的破坏，因此可能引发局部炎症反应，从而可能影响脱髓鞘和再髓鞘形成。为了研究这样的后果，我们应用立体定向注射在脱髓鞘脱髓鞘和再脱髓鞘是独立于这一程序介导的cuprizone模型。免疫组化检测注射区淋巴细胞和活化胶质细胞的存在。血蛋白染色用于评估血脑屏障的完整性，髓磷脂染色用于评估脱髓鞘和再髓鞘形成过程。立体定向注射导致血脑屏障局部破坏，表现为局部血蛋白外渗。沿注射管可检出T淋巴细胞和B淋巴细胞，并有较高的小胶质细胞增生和星形细胞增多的趋势。然而，这些变化并不影响注射部位、胼胝体或大脑皮层的脱髓鞘和再脱髓鞘过程。我们的研究结果表明，局部立体定向注射对中枢神经系统脱髓鞘和再髓鞘形成没有重大影响。
Remyelination is the natural repair mechanism in demyelinating disorders of the central nervous system (CNS) such as multiple sclerosis. Several animal models have been used to study demyelination and remyelination. Among toxic animal models, oral administration of the toxin cuprizone leads to white and gray matter demyelination. In contrast, focal demyelination models include the stereotactic application of a toxin such as lysolecithin or ethidium bromide. The injection procedure generates a local disruption of the blood-brain barrier (BBB) and might thus trigger a local inflammatory reaction and consequently may influence demyelination and remyelination. In order to study such consequences, we applied stereotactic injections in the cuprizone model where demyelination and remyelination are mediated independent of this procedure. Immunohistochemistry was performed to detect the presence of lymphocytes and activated glial cells in the injection area. Blood protein stainings were used to assess the integrity of the BBB and myelin staining to evaluate demyelination and remyelination processes. Stereotactic injection led to a local disruption of the BBB as shown by local extravasation of blood proteins. Along the injection canal, T and B lymphocytes could be detected and there was a tendency of a higher microgliosis and astrocytosis. However, these changes did not influence demyelination and remyelination processes at the site of injection, in the corpus callosum, or in the cerebral cortex. Our results suggest that a local stereotactic injection has no major impact on CNS demyelination and remyelination.