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

Hydrogen gas (H-2) 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 H-2 in moderate (120 min hypoxia) and severe (150 min hypoxia) neonatal HI rat models. We hypothesized that H-2 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 + H-2 n = 86). We also tested H-2 in middle cerebral artery occlusion (MCAO) in adult rats (MCAO n = 9, MCAO + H-2 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 H-2) was not associated with decreased volume of infarction or decreased concentration of MDA. H-2 gas pretreatment (2.9%) was associated with increased infarction volume in neonatal HI. In MCAO in adult rats, H-2 gas therapy demonstrated a trend of beneficial effect. Exposure of H-2 gas to non-ischemic neonates resulted in a significant increase in brain concentration of MDA. We conclude that 2.9% H-2 gas therapy does not ameliorate moderate to severe ischemic damage in neonatal hypoxia-ischemia. (C) 2008 Elsevier B.V. All rights reserved.