Antenatal Allopurinol Reduces Hippocampal Brain Damage After Acute Birth Asphyxia in Late Gestation Fetal Sheep

被引：16
|
作者：
Kaandorp, Joepe J. [1 ]
Derks, Jan B. [1 ]
Oudijk, Martijn A. [1 ]
Torrance, Helen L. [1 ]
Harmsen, Marline G. [1 ]
Nikkels, Peter G. J. [2 ]
van Bel, Frank [1 ]
Visser, Gerard H. A. [1 ]
Giussani, Dino A. [3 ]
机构：
[1] Univ Med Ctr, Perinatal Ctr, Utrecht, Netherlands
[2] Univ Med Ctr, Dept Pathol, Utrecht, Netherlands
[3] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England
来源：
REPRODUCTIVE SCIENCES | 2014年 / 21卷 / 02期
基金：
英国生物技术与生命科学研究理事会;
关键词：
sheep; fetus; asphyxia; allopurinol; neuroprotection; UMBILICAL-CORD OCCLUSION; HYPOXIC-ISCHEMIC ENCEPHALOPATHY; PERINATAL ASPHYXIA; XANTHINE-OXIDASE; NEAR-TERM; NEONATAL ENCEPHALOPATHY; OXIDATIVE STRESS; BLOOD-LEVELS; INJURY; PRETERM;
D O I：
10.1177/1933719113493516
中图分类号：
R71 [妇产科学];
学科分类号：
100211 ;
摘要：
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.
引用
收藏
页码：251 / 259
页数：9
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