BackgroundTerm and near-term infants are at high risk of developing brain injury and life-long disability if they have suffered from severe perinatal asphyxia. We hypothesized that propofol administration to the maternal-fetal unit can diminish cerebral injury in term and near-term infant fetuses in states of progressive severe asphyxia.MethodsForty-four late preterm lambs underwent total umbilical cord occlusion (UCO) or sham treatment in utero. UCO resulted in global asphyxia and cardiac arrest. After emergency cesarean section under either maternal propofol or isoflurane anesthesia, the fetuses were resuscitated and subsequently anesthetized the same way as their mothers.ResultsAsphyctic lambs receiving isoflurane showed a significant increase of total and low-frequency spectral power in bursts indicating seizure activity and more burst-suppression with a marked increase of interburst interval length during UCO. Asphyctic lambs receiving propofol showed less EEG changes. Propofol increased levels of anti-apoptotic B-cell lymphoma-extra large (Bcl-xL) and phosphorylated STAT-3 and reduced the release of cytochrome c from the mitochondria and the protein levels of activated cysteinyl aspartate-specific protease (caspase)-3, -9, and N-methyl-d-aspartate (NMDA) receptor.ConclusionsImprovement of fetal EEG during and after severe asphyxia could be achieved by propofol treatment of the ovine maternal-fetal unit. The underlying mechanism is probably the reduction of glutamate-induced cytotoxicity by down-regulation of NMDA receptors and an inhibition of the mitochondrial apoptotic pathway.

中文翻译：

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丙泊酚对母胎单位给药改善胎儿脑电图并影响严重窒息早产羔羊的脑凋亡途径

背景足月和近足月婴儿如果遭受严重的围产期窒息，极有可能发生脑损伤和终生残疾。我们假设在进行性严重窒息状态下，向母胎单元施用丙泊酚可以减少足月和近足月婴儿的脑损伤。方法 44 只晚期早产羔羊在子宫内接受了全脐带闭塞 (UCO) 或假治疗。UCO 导致全身窒息和心脏骤停。在产妇丙泊酚或异氟醚麻醉下紧急剖宫产后，胎儿复苏，随后以与母亲相同的方式麻醉。结果 接受异氟醚的窒息羔羊在爆发中显示出总和低频频谱功率的显着增加，表明癫痫发作活动和更多的爆发抑制，UCO 期间爆发间间隔长度显着增加。接受丙泊酚的窒息羔羊显示较少的脑电图变化。丙泊酚增加了抗凋亡 B 细胞淋巴瘤-超大 (Bcl-xL) 和磷酸化 STAT-3 的水平，并减少了线粒体中细胞色素 c 的释放和活化的半胱氨酸天冬氨酸特异性蛋白酶 (caspase)-3 的蛋白质水平、-9和N-甲基-d-天冬氨酸(NMDA)受体。结论通过丙泊酚处理绵羊母胎单元可以改善严重窒息期间和之后胎儿的EEG。