1Perinatal Center, University Medical Center, Utrecht, the Netherlands.
Reprod Sci. 2014 Feb;21(2):251-9. doi: 10.1177/1933719113493516. Epub 2013 Jun 21.
Free radical-induced reperfusion injury is a recognized cause of brain damage in the newborn after birth asphyxia. The xanthine oxidase inhibitor allopurinol reduces free radical synthesis and crosses the placenta easily. Therefore, allopurinol is a promising therapeutic candidate. This study tested the hypothesis that maternal treatment with allopurinol during fetal asphyxia limits ischemia-reperfusion (I/R) damage to the fetal brain in ovine pregnancy. The I/R challenge was induced by 5 repeated measured compressions of the umbilical cord, each lasting 10 minutes, in chronically instrumented fetal sheep at 0.8 of gestation. Relative to control fetal brains, the I/R challenge induced significant neuronal damage in the fetal hippocampal cornu ammonis zones 3 and 4. Maternal treatment with allopurinol during the I/R challenge restored the fetal neuronal damage toward control scores. Maternal treatment with allopurinol offers potential neuroprotection to the fetal brain in the clinical management of perinatal asphyxia.
自由基诱导的再灌注损伤是新生儿出生窒息后脑损伤的公认原因。黄嘌呤氧化酶抑制剂别嘌呤醇可减少自由基的合成，且容易穿过胎盘。因此，别嘌呤醇是一种很有前途的治疗候选药物。本研究旨在检验以下假设：在胎儿窒息期间对母体进行别嘌呤醇治疗可限制胎儿脑在羊胎妊娠中的缺血再灌注（I/R）损伤。通过对 0.8 孕周的慢性仪器化胎儿羊进行 5 次重复的脐带压迫，每次持续 10 分钟，来诱导 I/R 挑战。与对照胎儿大脑相比，I/R 挑战导致胎儿海马角 3 和 4 区的神经元损伤显著。在 I/R 挑战期间对母体进行别嘌呤醇治疗可使胎儿神经元损伤恢复到对照评分。在围产期窒息的临床管理中，对母体进行别嘌呤醇治疗可为胎儿大脑提供潜在的神经保护作用。
