Petersson Katherine H, Pinar Halit, Stopa Edward G, Faris Ronald A, Sadowska Grazyna B, Hanumara R Choudry, Stonestreet Barbara S
Department of Pediatrics, Brown University School of Medicine, Providence, Rhode Island 02906, USA.
Pediatr Res. 2002 Jun;51(6):768-76. doi: 10.1203/00006450-200206000-00019.
The effects of cerebral ischemia on white matter changes in ovine fetuses were examined after exposure to bilateral carotid artery occlusion. Fetal sheep were exposed to 30 min of ischemia followed by 48 (I/R-48, n = 8) or 72 (I/R-72, n = 10) h of reperfusion or control sham treatment (control, n = 4). Serial coronal sections stained with Luxol fast blue/hematoxylin and eosin were scored for white matter, cerebral cortical, and hippocampal lesions. All areas received graded pathologic scores of 0 to 5, reflecting the degree of injury where 0 = 0%, 1 = 1% to 25%, 2 = 26% to 50%, 3 = 51% to 75%, 4 = 76% to 95%, and 5 = 96% to 100% of the area damaged. Dual-label immunofluorescence using antibodies against glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) were used to characterize white matter lesions. Basic fibroblast growth factor (FGF-2) was measured in the frontal cortex by ELISA. Results of the pathologic scores showed that the white matter of the I/R-72 (2.74 +/- 0.53, mean +/- SEM) was more (p < 0.05) damaged when compared with the control (0.80 +/- 0.33) group. Cortical lesions were greater (p < 0.05) in the I/R-48 (2.12 +/- 0.35) than the control (0.93 +/- 0.09) group. White matter lesions were characterized by reactive GFAP-positive astrocytes and a loss of MBP in oligodendrocytes. The ratio of MBP to GFAP decreased (p < 0.05) as a function of ischemia, indicative of a proportionally greater loss of MBP than GFAP. FGF-2 concentrations were higher (p < 0.05) in the I/R-72 than the control group and there was a direct correlation between the pathologic scores (PS) and FGF-2 concentrations (FGF-2 = e((1.6 PS-0.90)) + 743, n = 17, r = 0.73, p < 0.001). We conclude that carotid artery occlusion results in quantifiable white matter lesions that are associated with a loss of MBP from myelin, and that FGF-2, a purported mediator of recovery from brain injury in adult subjects, increases in concentration in proportion to the severity of brain damage in the fetus.
在双侧颈动脉闭塞后，研究了脑缺血对绵羊胎儿白质变化的影响。将胎羊暴露于30分钟的缺血状态，随后分别进行48小时（I/R-48，n = 8）或72小时（I/R-72，n = 10）的再灌注，或进行对照假手术处理（对照组，n = 4）。对用Luxol固蓝/苏木精和伊红染色的系列冠状切片进行白质、大脑皮质和海马损伤评分。所有区域的病理评分等级为0至5，反映损伤程度，其中0 = 0%，1 = 1%至25%，2 = 26%至50%，3 = 51%至75%，4 = 76%至95%，5 = 96%至100%的区域受损。使用抗胶质纤维酸性蛋白（GFAP）和髓鞘碱性蛋白（MBP）的抗体进行双标记免疫荧光，以表征白质损伤。通过酶联免疫吸附测定法（ELISA）测量额叶皮质中的碱性成纤维细胞生长因子（FGF-2）。病理评分结果显示，与对照组（0.80±0.33）相比，I/R-72组（2.74±0.53，平均值±标准误）的白质损伤更严重（p < 0.05）。I/R-48组（2.12±0.35）的皮质损伤比对照组（0.93±0.09）更严重（p < 0.05）。白质损伤的特征是反应性GFAP阳性星形胶质细胞和少突胶质细胞中MBP的丢失。MBP与GFAP的比值随着缺血程度的增加而降低（p < 0.05），表明MBP的丢失比例大于GFAP。I/R-72组的FGF-2浓度高于对照组（p < 0.05），并且病理评分（PS）与FGF-2浓度之间存在直接相关性（FGF-2 = e((1.6 PS - 0.90)) + 743，n = 17，r = 0.73，p < 0.001）。我们得出结论，颈动脉闭塞导致可量化的白质损伤，这与髓鞘中MBP的丢失有关，并且FGF-2（一种据称在成年受试者脑损伤恢复中起介导作用的物质）在胎儿中的浓度随着脑损伤严重程度的增加而成比例升高。
