Increased injury following intermittent fetal hypoxia-reoxygenation is associated with increased free radical production in fetal rabbit brain

Sidhartha Tan, Fen Zhou, Vance G. Nielsen, Ziwei Wang, Candece L. Gladson, Dale A. Parks

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Hypoxia associated with perinatal events can result in brain damage in the neonate. In labor and eclampsia, hypoxia can be intermittent, which may result in more severe damage than sustained hypoxia. The pathogenesis of brain injury in sustained ischemia involves free radical production; therefore, we investigated whether higher levels of free radicals contribute to the greater injury induced by repetitive ischemia. Brains were obtained from fetuses of near-term, pregnant rabbits subjected to repetitive ischemia- reperfusion (RIR), sustained uterine ischemia-reperfusion (IR), or a control protocol. Compared with controls, fetal brains from RIR or IR groups had more brain edema. Brains from RIR fetuses exhibited higher levels of lipid peroxidation, 3-nitrotyrosine, and nitrogen oxides, and lower total antioxidant capacity and cortical cellular viability than those of IR or control fetuses. Maternal administration of antioxidants following RIR and fetal bradycardia resulted in lower levels of fetal cortical and hippocampal cell death. Coadministration of Trolox and ascorbic acid resulted in less brain edema and liquefaction, and fewer hippocampal ischemic nuclei as compared with the saline control. Higher free radical production may be responsible for the greater fetal brain injury following repetitive hypoxia- reoxygenation. Maternal antioxidant treatment resulted in transplacental passage of antioxidants and amelioration of brain injury, and may be a viable clinical option following diagnosis of fetal distress.

Original languageEnglish (US)
Pages (from-to)972-981
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Volume58
Issue number9
DOIs
StatePublished - Sep 1999
Externally publishedYes

Keywords

  • Antioxidants
  • Ascorbic acid
  • Hippocampus
  • Oxidants
  • Vitamin E

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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