title: Antenatal allopurinol reduces hippocampal brain damage after acute birth asphyxia in late gestation fetal sheep.
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.
authors.affiliation: 1Perinatal Center, University Medical Center, Utrecht, the Netherlands.
authors.forename: Joepe J
authors.initials: JJ
authors.lastname: Kaandorp
authors.forename: Jan B
authors.initials: JB
authors.lastname: Derks
authors.forename: Martijn A
authors.initials: MA
authors.lastname: Oudijk
authors.forename: Helen L
authors.initials: HL
authors.lastname: Torrance
authors.forename: Marline G
authors.initials: MG
authors.lastname: Harmsen
authors.forename: Peter G J
authors.initials: PG
authors.lastname: Nikkels
authors.forename: Frank
authors.initials: F
authors.lastname: van Bel
authors.forename: Gerard H A
authors.initials: GH
authors.lastname: Visser
authors.forename: Dino A
authors.initials: DA
authors.lastname: Giussani
mesh_terms: D000493:Allopurinol / Q000008:administration & dosage*; D000818:Animals; D001238:Asphyxia Neonatorum / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011247:Pregnancy; D011295:Prenatal Care / Q000379:methods; D012756:Sheep
chemical_list: D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D000493:Allopurinol
keywords: allopurinol; asphyxia; fetus; neuroprotection; sheep