Therapeutic potential of hydrogen gas in the reduction of vascular leakage using a 5-day neonatal hypoxic-ischemic piglet model

Abstract Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of morbidity and mortality in newborns in both high- and low-income countries. The important determinants of its pathophysiology are neural cells and vascular components. In neonatal HIE, increased vascular permeability due to damage to the blood–brain barrier is associated with seizures and poor outcomes in both translational and clinical studies. In our previous studies, hydrogen gas (H2) improved the neurological outcome of HIE and ameliorated the cell death. In this study, we used albumin immunohistochemistry to assess if H2 inhalation effectively reduced the cerebral vascular leakage. Of 33 piglets subjected to a hypoxic-ischemic insult, 26 piglets were ultimately analyzed. After the insult, the piglets were grouped into normothermia (NT), H2 inhalation (H2), hypothermia (TH), and H2 with TH (H2-TH) groups. The albumin immunohistochemistry score was lowest in the H2 group and significantly lower than in the NT group, suggesting the ability of H2 gas alone to ameliorate HIE-associated vascular leakage. To prove the effectiveness of H2 in vascular leakage, further experimental studies of a specific insult severity and target cells are required.