UPLC-QTOF/MS-Based Metabolomics Reveals the Protective Mechanism of Hydrogen on Mice with Ischemic Stroke

As a reductive gas, hydrogen plays an antioxidant role by selectively scavenging oxygen free radicals. It has been reported that hydrogen has protective effects against nerve damage caused by ischemia–reperfusion in stroke, but the specific mechanism is still unclear. Therefore, this study aims to investigate the protective effects of hydrogen on stroke-induced ischemia– reperfusion injuryand its detailed mechanism. Two weeks after the inhalation of high concentrations (66.7%) of hydrogen, middle cerebral artery occlusion (MCAO) was induced in mice using the thread occlusion technique to establish an animal model of the focal cerebral ischemia–reperfusion. Then, a metabolomicsanalysis of mouse cerebral cortex tissues was first performed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) to study the metabolic changes and protective mechanisms of hydrogen on stroke ischemia– reperfusion injury. According to the metabolomicprofiling of cortex tissues, 29 different endogenous metabolites were screened, including palmitoyl-l- carnitine, citric acid, glutathione, taurine, acetyl-l-carnitine, N-acetylaspartylglutamic acid(NAAG), l-aspartic acid, lysophosphatidylcholine(LysoPC) and lysophosphatidylethanolamine(LysoPE). Through pathway analysis, the metabolic pathways were concentrate on the glutathione pathway and the taurinepathway, mitochondrial energy metabolism and phospholipid metabolism that related to the oxidative stress process. This result reveals that hydrogen may protect against ischemic stroke by reducing oxidative stress during ischemia–reperfusion, thereby protecting nerve cells from reactive oxygen species(ROS).