Hydrogen gas is ineffective in moderate and severe neonatal hypoxia-ischemia rat models

Gerald A. Matchett, Nancy Fathali, Yu Hasegawa, Vikram Jadhav, Robert P. Ostrowski, Robert D. Martin, Ihab R. Dorotta, Xuejun Sun, John H. Zhang

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Hydrogen gas (H2) has been shown to ameliorate brain injury in experimental adult rat focal ischemia and in a mild neonatal hypoxia-ischemia (HI, 90 min hypoxia) rat model. In this study we tested H2 in moderate (120 min hypoxia) and severe (150 min hypoxia) neonatal HI rat models. We hypothesized that H2 would improve outcomes after neonatal HI by scavenging free radicals. Two hundred (200) unsexed Sprague-Dawley rats at day 10 of life (p10) underwent neonatal HI with the Rice-Vannucci model. Multiple treatment protocols were studied, including pre-ischemic treatment, intra-ischemic treatment, and post-ischemic treatment (Sham n = 32, HI n = 82, HI + H2 n = 86). We also tested H2 in middle cerebral artery occlusion (MCAO) in adult rats (MCAO n = 9, MCAO + H2 n = 7) for comparison. Analysis at 24 h included infarction volume, measurement of brain concentration of malondialdehyde (MDA) (an end-product of lipid peroxidation), daily weight, Nissl histology, and mortality. In moderate and severe neonatal HI models, hydrogen gas therapy (2.9% concentration H2) was not associated with decreased volume of infarction or decreased concentration of MDA. H2 gas pretreatment (2.9%) was associated with increased infarction volume in neonatal HI. In MCAO in adult rats, H2 gas therapy demonstrated a trend of beneficial effect. Exposure of H2 gas to non-ischemic neonates resulted in a significant increase in brain concentration of MDA. We conclude that 2.9% H2 gas therapy does not ameliorate moderate to severe ischemic damage in neonatal hypoxia-ischemia.

Original languageEnglish (US)
Pages (from-to)90-97
Number of pages8
JournalBrain Research
Volume1259
DOIs
StatePublished - Mar 9 2009

Keywords

  • Free radical
  • H
  • Hydrogen gas
  • Neonatal hypoxia-ischemia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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    Matchett, G. A., Fathali, N., Hasegawa, Y., Jadhav, V., Ostrowski, R. P., Martin, R. D., Dorotta, I. R., Sun, X., & Zhang, J. H. (2009). Hydrogen gas is ineffective in moderate and severe neonatal hypoxia-ischemia rat models. Brain Research, 1259, 90-97. https://doi.org/10.1016/j.brainres.2008.12.066