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Acta Pharmacol Sin. 2018 Aug;39(8):1273-1283. doi: 10.1038/aps.2017.148. Epub 2018 Mar 22.

Molecular hydrogen alleviates asphyxia-induced neuronal cyclooxygenase-2 expression in newborn pigs.

Author information

1
Department of Physiology, University of Szeged, School of Medicine, Szeged, Hungary. varga.viktoria.eva@med.u-szeged.hu.
2
Department of Physiology, University of Szeged, School of Medicine, Szeged, Hungary.
3
Department of Pathology, University of Szeged, School of Medicine, Szeged, Hungary.

Abstract

Cyclooxygenase-2 (COX-2) has an established role in the pathogenesis of hypoxic-ischemic encephalopathy (HIE). In this study we sought to determine whether COX-2 was induced by asphyxia in newborn pigs, and whether neuronal COX-2 levels were affected by H2 treatment. Piglets were subjected to either 8 min of asphyxia or a more severe 20 min of asphyxia followed by H2 treatment (inhaling room air containing 2.1% H2 for 4 h). COX-2 immunohistochemistry was performed on brain samples from surviving piglets 24 h after asphyxia. The percentages of COX-2-immunopositive neurons were determined in cortical and subcortical areas. Only in piglets with more severe HIE, we observed significant, region-specific increases in neuronal COX-2 expression within the parietal and occipital cortices and in the CA3 hippocampal subfield. H2 treatment essentially prevented the increases in COX-2-immunopositive neurons. In the parietal cortex, the attenuation of COX-2 induction was associated with reduced 8'-hydroxy-2'-deoxyguanozine immunoreactivity and retained microglial ramifcation index, which are markers of oxidative stress and neuroinfiammation, respectively. This study demonstrates for the first time that asphyxia elevates neuronal COX-2 expression in a piglet HIE model. Neuronal COX-2 induction may play region-specific roles in brain lesion progression during HIE development, and inhibition of this response may contribute to the antioxidant/anti-infiammatory neuroprotective effects of H2 treatment.

KEYWORDS:

8′-hydroxy-2′-deoxyguanozine; COX-2; hypoxic-ischemic encephalopathy; microglia; molecular hydrogen; neuroprotection; newborn pigs

PMID:
29565041
PMCID:
PMC6289359
[Available on 2019-08-01]
DOI:
10.1038/aps.2017.148

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