The Fetal Physiology and Neuroscience Group, The Department of Physiology, The University of Auckland, Auckland, New Zealand.
J Physiol. 2018 Dec;596(23):6079-6092. doi: 10.1113/JP275627. Epub 2018 Apr 16.
We evaluated the effect of magnesium sulphate (MgSO ) on seizures induced by asphyxia in preterm fetal sheep. MgSO did not prevent seizures, but significantly reduced the total duration, number of seizures, seizure amplitude and average seizure burden. Saline-asphyxia male fetuses had significantly more seizures than female fetuses, but male fetuses showed significantly greater reduction in seizures during MgSO infusion than female fetuses. A circadian profile of seizure activity was observed in all fetuses, with peak seizures seen around 04.00-06.00 h on the first and second days after the end of asphyxia. This study is the first to demonstrate that MgSO has utility as an anti-seizure agent after hypoxia-ischaemia. More information is needed about the mechanisms mediating the effect of MgSO on seizures and sexual dimorphism, and the influence of circadian rhythms on seizure expression.
Seizures are common in newborns after asphyxia at birth and are often refractory to anti-seizure agents. Magnesium sulphate (MgSO ) has anticonvulsant effects and is increasingly given to women in preterm labour for potential neuroprotection. There is limited information on its effects on perinatal seizures. We examined the hypothesis that MgSO infusion would reduce fetal seizures after asphyxia in utero. Preterm fetal sheep at 0.7 gestation (104 days, term = 147 days) were given intravenous infusions of either saline (n = 14) or MgSO (n = 12, 160 mg bolus + 48 mg h infusion over 48 h). Fetuses underwent umbilical cord occlusion (UCO) for 25 min, 24 h after the start of infusion. The start time for seizures did not differ between groups, but MgSO significantly reduced the total number of seizures (P < 0.001), peak seizure amplitude (P < 0.05) and seizure burden (P < 0.005). Within the saline-asphyxia group, male fetuses had significantly more seizures than females (P < 0.05). Within the MgSO -asphyxia group, although both sexes had fewer seizures than the saline-asphyxia group, the greatest effect of MgSO was on male fetuses, with reduced numbers of seizures (P < 0.001) and seizure burden (P < 0.005). Only 1 out of 6 MgSO males had seizures on the second day post-UCO compared to 5 out of 6 MgSO female fetuses (P = 0.08). Finally, seizures showed a circadian profile with peak seizures between 04.00 and 06.00 h on the first and second day post-UCO. Collectively, these results suggest that MgSO may have utility in treating perinatal seizures and has sexually dimorphic effects.
我们评估了硫酸镁（MgSO）对窒息诱导的早产胎儿羊痫性发作的影响。MgSO 不能预防癫痫发作，但显著减少了癫痫发作的总持续时间、发作次数、发作幅度和平均发作负荷。盐水窒息的雄性胎儿比雌性胎儿有更多的癫痫发作，但在 MgSO 输注期间，雄性胎儿的癫痫发作减少程度显著大于雌性胎儿。所有胎儿均观察到癫痫发作的昼夜节律，在窒息结束后第 1 和第 2 天的 04:00-06:00 左右出现发作高峰。这项研究首次证明，MgSO 作为缺氧缺血后的抗惊厥药物具有一定的效用。需要更多关于 MgSO 对癫痫发作和性别二态性的作用机制以及昼夜节律对癫痫发作表达的影响的信息。
新生儿出生后窒息时癫痫发作很常见，且常对抗惊厥药物有抗药性。硫酸镁（MgSO）具有抗惊厥作用，越来越多地用于有早产风险的孕妇以提供潜在的神经保护。关于其对围产期癫痫发作的影响，信息有限。我们检验了 MgSO 输注可减少宫内窒息后胎儿癫痫发作的假设。妊娠 0.7 期（104 天，足月=147 天）的早产胎儿接受静脉内输注盐水（n=14）或 MgSO（n=12，160mg 推注+48mg/h 输注 48 小时）。胎儿在输注开始后 24 小时进行脐带结扎（UCO）25 分钟。两组的癫痫发作起始时间无差异，但 MgSO 显著减少了癫痫发作的总次数（P<0.001）、峰值癫痫发作幅度（P<0.05）和发作负荷（P<0.005）。在盐水窒息组中，雄性胎儿的癫痫发作次数明显多于雌性胎儿（P<0.05）。在 MgSO-窒息组中，尽管两性的癫痫发作次数均少于盐水窒息组，但 MgSO 的最大作用是对雄性胎儿，减少了癫痫发作的次数（P<0.001）和发作负荷（P<0.005）。与 6 只 MgSO 雄性胎儿中的 1 只相比，6 只 MgSO 雌性胎儿中有 5 只在 UCO 后第 2 天出现癫痫发作（P=0.08）。最后，癫痫发作呈现昼夜节律，第 1 和第 2 天 UCO 后 04:00-06:00 之间出现发作高峰。总之，这些结果表明，MgSO 可能对治疗围产期癫痫发作有效，且具有性别二态作用。
