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Intrauterine Growth Restriction and Hyperoxia as a Cause of White Matter Injury.
Developmental Neuroscience ( IF 2.9 ) Pub Date : 2018-11-15 , DOI: 10.1159/000494273
Jill L Chang 1 , Mirrah Bashir 2 , Christiana Santiago 3 , Kathryn Farrow 2 , Camille Fung 4 , Ashley S Brown 4 , Robert W Dettman 5 , Maria L V Dizon 2
Affiliation  

Intrauterine growth restriction (IUGR) is estimated to occur in 5% of pregnancies, with placental insufficiency being the most common cause in developed countries. While it is known that white matter injury occurs in premature infants, the extent of IUGR on white matter injury is less defined in term infants. We used a novel murine model that utilizes a thromboxane A2 (TXA2) analog (U46619), a potent vasoconstrictor, to induce maternal hypertension and mimic human placental insufficiency-induced IUGR to study the white matter. We also investigated the role of hyperoxia as an additional risk factor for white matter injury, as IUGR infants are at increased risk of respiratory comorbidities leading to increased oxygen exposure. We found that TXA2 analog-induced IUGR results in white matter injury as demonstrated by altered myelin structure and changes in the oligodendroglial cell/oligodendrocyte population. In addition, our study demonstrates that hyperoxia exposure independently results in white matter perturbation. To our knowledge, this is the first study to report single and combined effects of IUGR with hyperoxia impacting the white matter and motor function. These results draw attention to the need for close monitoring of motor development in IUGR babies following hospital discharge as well as highlighting the importance of limiting, as clinically feasible, the degree of oxygen overexposure to potentially improve motor outcomes in this population of infants.

中文翻译:

宫内生长受限和高氧血症是白色物质损伤的原因。

宫内生长受限(IUGR)估计发生在5%的妊娠中,胎盘功能不全是发达国家中最常见的原因。虽然已知早产儿会发生白质损伤,但足月婴儿对IUGR引起的白质损伤的程度定义较少。我们使用了一种新型的小鼠模型,该模型利用血栓烷A2(TXA2)类似物(U46619)(一种有效的血管收缩剂)来诱导孕产妇高血压并模仿人胎盘供血不足引起的IUGR来研究白质。我们还调查了高氧作为白质损伤的另一个危险因素的作用,因为IUGR婴儿的呼吸系统合并症风险增加,导致氧气暴露增加。我们发现TXA2类似物诱导的IUGR导致白质损伤,如髓鞘结构改变和少突胶质细胞/少突胶质细胞群体的变化所证实。此外,我们的研究表明,高氧暴露会独立导致白质摄动。据我们所知,这是第一个报告IUGR与高氧影响白质和运动功能的单一和联合作用的研究。这些结果引起了人们对出院后IUGR婴儿运动发育的密切监测的需要的关注,并强调了限制(在临床上可行的)限制氧气过度暴露的程度以潜在地改善这种婴儿运动能力的重要性。我们的研究表明,高氧暴露独立导致白质摄动。据我们所知,这是第一个报告IUGR与高氧影响白质和运动功能的单一和联合作用的研究。这些结果引起了人们对出院后IUGR婴儿运动发育的密切监测的需要的关注,并强调了限制(在临床上可行的)限制氧气过度暴露的程度以潜在地改善这种婴儿运动能力的重要性。我们的研究表明,高氧暴露独立导致白质摄动。据我们所知,这是第一个报告IUGR与高氧影响白质和运动功能的单一和联合作用的研究。这些结果引起了人们对出院后IUGR婴儿运动发育的密切监测的需要的关注,并强调了限制(在临床上可行的)限制氧气过度暴露的程度以潜在地改善这种婴儿运动能力的重要性。
更新日期:2019-11-01
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