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

Abstract

Using a neonatal piglet model of hypoxic-ischemic encephalopathy (HIE), this study examined whether asphyxia induces neuronal cyclooxygenase-2 (COX-2) and whether H2 inhalation modifies this response. Piglets underwent either 8 or 20 minutes of asphyxia, followed by inhalation of room air containing 2.1% H2 for 4 hours. Immunohistochemical analysis at 24 hours post-asphyxia revealed that severe HIE produced region-specific increases in COX-2-positive neurons within the parietal and occipital cortices and the CA3 hippocampal subfield. H2 inhalation substantially prevented these elevations. In the parietal cortex, reduced 8-hydroxy-2'-deoxyguanosine immunoreactivity and preserved microglial ramification index accompanied the attenuation of COX-2 induction, indicating concurrent reductions in oxidative stress and neuroinflammation. These findings establish that asphyxia elevates neuronal COX-2 in a region-dependent manner, and that H2 inhalation suppresses this pathway, potentially contributing to its neuroprotective properties.

Mechanism

H2 inhalation appears to suppress asphyxia-induced neuronal COX-2 upregulation by reducing oxidative stress (evidenced by decreased 8-OHdG immunoreactivity) and attenuating neuroinflammation (reflected by preserved microglial ramification), thereby limiting region-specific brain lesion progression in HIE.