Conflicting findings on the effectiveness of hydrogen therapy for ameliorating vascular leakage in a 5-day post hypoxic-ischemic survival piglet model

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 (H-2) improved the neurological outcome of HIE and ameliorated the cell death. In this study, we used albumin immunohistochemistry to assess if H-2 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), H-2 ventilation (H-2), therapeutic hypothermia (TH), and H-2 combined with TH (H-2-TH) groups. The ratio of albumin stained to unstained areas was analyzed and found to be lower in the H-2 group than in the other groups, although the difference was not statistically significant. In this study, H-2 therapy did not significantly improve albumin leakage despite the histological images suggesting signs of improvement. Further investigations are warranted to study the efficacy of H-2 gas for vascular leakage in neonatal HIE.

Automated summary

Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of morbidity and mortality in newborns worldwide. This study investigated the efficacy of hydrogen gas (H-2) in reducing cerebral vascular leakage using albumin immunohistochemistry in piglets subjected to a hypoxic-ischemic insult. Although histological images suggested signs of improvement, H-2 therapy did not significantly reduce albumin leakage in this study. Further investigations are needed to determine the effectiveness of H-2 gas for vascular leakage in neonatal HIE.