Antenatal allopurinol reduces hippocampal brain damage after acute birth asphyxia in late gestation fetal sheep

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.

Keywords: allopurinol; asphyxia; fetus; neuroprotection; sheep.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol / administration & dosage*
  • Animals
  • Asphyxia Neonatorum / complications
  • Asphyxia Neonatorum / drug therapy*
  • Asphyxia Neonatorum / pathology
  • Brain Injuries / etiology
  • Brain Injuries / pathology
  • Brain Injuries / prevention & control*
  • Female
  • Free Radical Scavengers / administration & dosage
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Neuroprotective Agents / administration & dosage*
  • Pregnancy
  • Prenatal Care / methods
  • Sheep


  • Free Radical Scavengers
  • Neuroprotective Agents
  • Allopurinol