Castillo-Meléndez Margie, Chow Jo Ann, Walker David W
Department of Physiology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia, 3800.
Pediatr Res. 2004 May;55(5):864-71. doi: 10.1203/01.PDR.0000115679.86566.C4. Epub 2004 Feb 5.
Umbilical cord occlusion (UCO), a known risk factor for perinatal brain damage, causes severe fetal asphyxia leading to oxidative stress, lipid peroxidation, and cell death. We have determined the effects of two 10-min UCO on the distribution of the lipid peroxidation marker 4-hydroxynonenal (4-HNE) and the activated form of the apoptosis marker caspase-3 in the brains of late-gestation fetal sheep. UCO caused asphyxia, hypertension, and bradycardia, but these parameters normalized 2 h after the occlusion. At postmortem, 48 h after the second UCO there were significantly higher numbers of 4-HNE-positive cells in all layers of the hippocampus and cerebellum, the parietal cortex, substantia nigra, caudate nucleus, putamen, and thalamus compared with control brains. 4-HNE immunoreactivity was also found in white matter tracts of the subcallosal bundle, external medullary lamina, reticular thalamic nucleus, and cerebellar fiber tracts only in UCO brains. Double-labeling identified these cells as predominantly neurons and astrocytes, with oligodendrocytes showing lower levels of 4-HNE immunoreactivity. After UCO, the number of caspase-3-immunopositive cells was increased significantly in the hippocampal CA1, molecular layer and dentate gyrus, ventrolateral thalamic nucleus, substantia nigra, putamen, and cerebellar granular and molecular layers compared with controls. Double-labeling revealed caspase-3 immunoreactivity was mainly in neurons, and to lesser extent in astrocytes and oligodendrocytes. Pyknotic cell numbers were significantly increased in hippocampal CA1 and CA3, parietal cortex, caudate nucleus, putamen, and cerebellar Purkinje cells after UCO. These data indicate that brief asphyxia induces widespread lipid peroxidation involving all cell types of the fetal brain and apoptosis in both neurons and glia.
脐带闭塞（UCO）是围产期脑损伤的已知危险因素，可导致严重的胎儿窒息，进而引发氧化应激、脂质过氧化和细胞死亡。我们已经确定了两次10分钟的脐带闭塞对妊娠晚期胎羊大脑中脂质过氧化标志物4-羟基壬烯醛（4-HNE）的分布以及凋亡标志物半胱天冬酶-3的活化形式的影响。脐带闭塞导致窒息、高血压和心动过缓，但这些参数在闭塞后2小时恢复正常。在第二次脐带闭塞后48小时进行尸检时，与对照大脑相比，海马体、小脑、顶叶皮质、黑质、尾状核、壳核和丘脑各层中4-HNE阳性细胞的数量显著增加。仅在脐带闭塞的大脑中，在胼胝体下束、外髓板、丘脑网状核和小脑纤维束的白质束中也发现了4-HNE免疫反应性。双重标记确定这些细胞主要为神经元和星形胶质细胞，少突胶质细胞的4-HNE免疫反应性水平较低。脐带闭塞后，与对照组相比，海马CA1区、分子层和齿状回、腹外侧丘脑核、黑质、壳核以及小脑颗粒层和分子层中半胱天冬酶-3免疫阳性细胞的数量显著增加。双重标记显示半胱天冬酶-3免疫反应性主要存在于神经元中，在星形胶质细胞和少突胶质细胞中的程度较小。脐带闭塞后，海马CA1区和CA3区、顶叶皮质、尾状核、壳核以及小脑浦肯野细胞中的固缩细胞数量显著增加。这些数据表明，短暂的窒息会诱导胎儿大脑所有细胞类型广泛的脂质过氧化以及神经元和神经胶质细胞的凋亡。
