Souza-Rodrigues R D, Costa A M R, Lima R R, Dos Santos C D, Picanço-Diniz C W, Gomes-Leal W
Laboratory of Experimental Neuroprotection and Neuroregeneration, Department of Morphology, Biological Sciences Center, Federal University of Pará, Belém-Pará, Brazil.
Brain Res. 2008 Mar 20;1200:78-88. doi: 10.1016/j.brainres.2007.11.025. Epub 2007 Nov 22.
Following acute and chronic neurodegenerative disorders, a cascade of pathological events including inflammatory response, excitotoxicity and oxidative stress induces secondary tissue loss in both gray and white matter. Axonal damage and demyelination are important components of the white matter demise during these diseases. In spite of this, a few studies have addressed the patterns of inflammatory response, axonal damage and demyelination following focal ischemic damage to the central nervous system (CNS). In the present study, we describe the patterns of inflammatory response, axonal damage and myelin impairment following microinjections of 10 pmol of endothelin-1 into the rat striatum. Animals were perfused at 1 day, 3 days and 7 days after injection. 20 mum sections were stained by hematoxylin and immunolabeled for neutrophils (anti-MBS-1), activated macrophages/microglia (anti-ED1), damaged axons (anti-betaAPP) and myelin (anti-MBP). The evolution of acute inflammation was quantitatively assessed by cell counts in different survival times. There was recruitment of both neutrophils and macrophages to the damaged striatal parenchyma with maximum recruitment at 1 day and 7 days, respectively. Progressive myelin impairment in the striatal white matter tracts has been observed mainly at later survival times. beta-APP+ endbulbs were not present in all evaluated time points. These results suggest that progress myelin impairment in the absence of damage to axonal cylinder is a feature of white matter pathology following endothelin-1-induced focal striatal ischemia.
在急性和慢性神经退行性疾病之后，一系列病理事件，包括炎症反应、兴奋性毒性和氧化应激，会导致灰质和白质的继发性组织损失。轴突损伤和脱髓鞘是这些疾病中白质损伤的重要组成部分。尽管如此，很少有研究探讨中枢神经系统（CNS）局灶性缺血损伤后炎症反应、轴突损伤和脱髓鞘的模式。在本研究中，我们描述了向大鼠纹状体微量注射10 pmol内皮素-1后炎症反应、轴突损伤和髓鞘损伤的模式。在注射后1天、3天和7天对动物进行灌注。将20μm切片用苏木精染色，并对中性粒细胞（抗MBS-1）、活化的巨噬细胞/小胶质细胞（抗ED1）、受损轴突（抗β淀粉样前体蛋白）和髓鞘（抗髓鞘碱性蛋白）进行免疫标记。通过不同存活时间的细胞计数对急性炎症的演变进行定量评估。中性粒细胞和巨噬细胞均募集到受损的纹状体实质，分别在1天和7天募集最多。主要在存活后期观察到纹状体白质束的进行性髓鞘损伤。在所有评估时间点均未出现β淀粉样前体蛋白阳性终球。这些结果表明，在内皮素-1诱导的局灶性纹状体缺血后，在轴突圆柱体未受损的情况下进行性髓鞘损伤是白质病理的一个特征。
