Antenatal Allopurinol Reduces Hippocampal Brain Damage After Acute Birth Asphyxia in Late Gestation Fetal Sheep. (February 2014)

• Record Type: Journal Article
• Authors: Kaandorp, Joepe J.; Derks, Jan B.; Oudijk, Martijn A.; Torrance, Helen L.; Harmsen, Marline G.; Nikkels, Peter G. J.; Bel, Frank van; Visser, Gerard H. A.; Giussani, Dino A.
• Is Part Of: Reproductive sciences. Volume 21:Number 2(2014:Feb.)
• Page Start: 251
• Page End: 259
• Publication Date: 2014-02
• Subjects: sheep -- fetus -- asphyxia -- allopurinol -- neuroprotection; Reproductive health -- Periodicals; Reproduction -- Periodicals; 612.6
• DOI: 10.1177/1933719113493516
• Languages: English
• ISSNs: 1933-7191

Abstract

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.