Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Wendlingweg 2, 52074, Aachen, Germany.
J Mol Neurosci. 2012 Sep;48(1):66-76. doi: 10.1007/s12031-012-9773-x. Epub 2012 Apr 22.
Brain inflammation plays a central role in multiple sclerosis (MS). Besides lymphocytes, the astroglia and microglia mainly contribute to the cellular composition of the inflammatory infiltrate in MS lesions. Several studies were able to demonstrate that cortical lesions are characterized by lower levels of inflammatory cells among activated microglia/macrophages. The underlying mechanisms for this difference, however, remain to be clarified. In the current study, we compared the kinetics and extent of microglia and astrocyte activation during early and late cuprizone-induced demyelination in the white matter tract corpus callosum and the telencephalic gray matter. Cellular parameters were related to the expression profiles of the chemokines Ccl2 and Ccl3. We are clearly able to demonstrate that both regions are characterized by early oligodendrocyte stress/apoptosis with concomitant microglia activation and delayed astrocytosis. The extent of microgliosis/astrocytosis appeared to be greater in the subcortical white matter tract corpus callosum compared to the gray matter cortex region. The same holds true for the expression of the key chemokines Ccl2 and Ccl3. The current study defines a model to study early microglia activation and to investigate differences in the neuroinflammatory response of white vs. gray matter.
脑炎症在多发性硬化症（MS）中起着核心作用。除淋巴细胞外，星形胶质细胞和小胶质细胞主要促成 MS 病变中炎症浸润的细胞组成。几项研究能够证明皮质病变的特点是活化的小胶质细胞/巨噬细胞中炎症细胞水平较低。然而，这种差异的潜在机制仍有待阐明。在本研究中，我们比较了早期和晚期 cuprizone 诱导的脱髓鞘过程中，在白质束胼胝体和大脑灰质中，小胶质细胞和星形胶质细胞激活的动力学和程度。细胞参数与趋化因子 Ccl2 和 Ccl3 的表达谱相关。我们能够清楚地证明，这两个区域的特征都是早期少突胶质细胞应激/凋亡，伴有小胶质细胞激活和迟发性星形胶质细胞增生。与灰质皮层区域相比，在皮质下白质束胼胝体中，小胶质细胞增生/星形胶质细胞增生的程度似乎更大。关键趋化因子 Ccl2 和 Ccl3 的表达也是如此。本研究定义了一个模型，用于研究早期小胶质细胞激活，并研究白质与灰质之间神经炎症反应的差异。
