Brain Injury Caused by Chronic Fetal Hypoxemia Is Mediated by Inflammatory Cascade Activation
Brain Injury Caused by Chronic Fetal Hypoxemia Is Mediated by Inflammatory Cascade Activation
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DOI：
10.1177/1933719110364061
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发表时间：
2010-06-01
影响因子：
2.9
通讯作者：
Weiner, Carl P.
中科院分区：
文献类型：
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作者：
Guo, Rong;Hou, Weijian;Weiner, Carl P.
脑性瘫痪(CP)的患病率在时间和地理上几乎没有变化，与早产、母婴感染/炎症和胎儿生长受限(IUGR)有关，IUGR是慢性胎儿低氧血症(CHX)的潜在替代品。我们之前证明了CHX会导致胎儿炎症反应综合征(FIFS)。在此，我们验证了CHX可能通过上调炎性细胞因子的级联反应，最终导致细胞凋亡途径激活而导致胎儿脑损伤的假设。时间交配的豚鼠饲养在12%或10.5%O-2中，直到妊娠的最后21%。慢性胎儿低氧血症增加了乳酸/丙酮酸，降低了谷胱甘肽(GSH)/氧化谷胱甘肽(GSSH)的比值，证实了向促氧化状态的转变。最终结果是海马神经元密度下降了30%。基于含有113种细胞因子和受体的微阵列，CHX与缺氧程度成比例地上调了22个基因；定量聚合酶链式反应(PCR)证实了这一发现。因此，CHX引发胎儿脑部炎症的程度与其严重程度成反比，其特点是细胞凋亡和神经元丢失增加。我们认为CHX胎儿脑损伤不是由氧气恶化直接引起的，而是一种适应性反应，变得不适应。
The prevalence of cerebral palsy (CP) shows little temporal or geographic variation and is associated with preterm birth, maternal/fetal infection/inflammation, and fetal growth restriction (IUGR), a potential surrogate for chronic fetal hypoxemia (CHX). We previously demonstrated CHX causes a fetal inflammatory response syndrome (FIRS). Herein, we test the hypothesis that CHX may cause fetal brain injury by upregulating inflammatory cytokine cascades, culminating in apoptosis pathway activation. Time-mated guinea pigs were housed in 12% or 10.5% O-2 for the last 21% of gestation. Chronic fetal hypoxemia increased the lactate/pyruvate and decreased the glutathione (GSH)/oxidized glutathione (GSSH) ratios, confirming a shift to a prooxidant state. The end result was a > 30% decrease in hippocampal neuron density. Based on a microarray spotted with 113 cytokines and receptors, 22 genes were upregulated by CHX in proportion to the degree of hypoxia; the findings were confirmed by quantitative polymerase chain reaction (PCR). Thus, CHX triggers fetal brain inflammation inversely proportional to its severity characterized by increased apoptosis and neuronal loss. We suggest CHX fetal brain injury is not directly caused by oxygen depravation but rather is an adaptive response that becomes maladaptive.