Article

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

Authors: Viktória VARGA1, János NÉMETH1, Orsolya OLÁH2, Valéria TóTh-Szűki1, Viktória kovácS1, Gábor RemzSő1, Ferenc Domoki1
1 Department of Physiology, University of Szeged, School of Medicine, Szeged, Hungary
2 Department of Pathology, University of Szeged, School of Medicine, Szeged, Hungary
Corresponding to: Viktória VARGA: varga.viktoria.eva@med.u-szeged.hu,
DOI: 10.1038/aps.2017.148
Received: 3 August 2017
Accepted: 8 November 2017
Advance online: 22 March 2018

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 neuroinflammation, 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-inflammatory neuroprotective effects of H2 treatment.
Keywords: hypoxic-ischemic encephalopathy; COX-2; 8’-hydroxy-2’-deoxyguanozine; microglia; molecular hydrogen; neuroprotection; newborn pigs