Fetal brain sparing in a mouse model of chronic maternal hypoxia
Fetal brain sparing in a mouse model of chronic maternal hypoxia
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DOI：
10.1177/0271678x17750324
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发表时间：
2019-06-01
影响因子：
6.3
通讯作者：
Sled, John G.
中科院分区：
文献类型：
--
作者：
Cahill, Lindsay S.;Hoggarth, Johnathan;Sled, John G.
低颅压是人类妊娠期间常见的现象，但对其对胎儿大脑的影响知之甚少。本研究探讨了胎儿血流动力学的反应，慢性缺氧的实验小鼠模型的母亲慢性缺氧（11%O-2从E14.5到E17.5）。使用高频多普勒超声，我们发现胎儿大脑和静脉导管血流量都增加了69%，肺血流量减少了62%，在胎儿暴露于慢性缺氧与对照组相比。这表明，在慢性胎儿缺氧期间，脑保护持续存在，并且由“流动”介导，其中高度含氧的血液优先通过静脉导管流向脑循环，绕过肝脏和肺部。与这些血流变化一致，通过MRI测量的胎儿脑体积保持不变，而肝脏和肺体积与对照组相比减少。然而，缺氧暴露的胎儿容易受到急性缺氧挑战（8%O-2 3分钟），表明全球血流减少与即将到来的胎儿死亡，而不是脑血流量升高。尽管存在这种脆弱性，但与对照组相比，暴露于慢性母体缺氧的小鼠的成年脑形态没有差异。
Hypoxic stress is a common occurrence during human pregnancy, yet little is known about its effects on the fetal brain. This study examined the fetal hemodynamic responses to chronic hypoxia in an experimental mouse model of chronic maternal hypoxia (11% O-2 from E14.5 to E17.5). Using high-frequency Doppler ultrasound, we found fetal cerebral and ductus venosus blood flow were both elevated by 69% and pulmonary blood flow was decreased by 62% in the fetuses exposed to chronic hypoxia compared to controls. This demonstrates that brain sparing persists during chronic fetal hypoxia and is mediated by "streaming," where highly oxygenated blood preferentially flows through the ductus venosus towards the cerebral circulation, bypassing the liver and the lungs. Consistent with these changes in blood flow, the fetal brain volume measured by MRI is preserved, while the liver and lung volumes decreased compared to controls. However, hypoxia exposed fetuses were rendered vulnerable to an acute hypoxic challenge (8% O-2 for 3 min), demonstrating global blood flow decreases consistent with imminent fetal demise rather than elevated cerebral blood flow. Despite this vulnerability, there were no differences in adult brain morphology in the mice exposed to chronic maternal hypoxia compared to controls.