In situ analysis of metabolic changes under hypoxic-ischemic encephalopathy via MALDI mass spectrometry imaging

Abstract

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neurological disability and even more serious fetal or neonatal asphyxia death. As the therapeutic time window is limited and timely intervention could have a better prognosis, elucidating the mechanisms underlying HIE and developing novel therapeutic strategies is of great importance. In the present study, 1, 5-Diaminonaphthalene hydrochloride (1, 5-DANHCl) assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was applied to the neonatal rat model of HIE to investigate metabolic changes during hypoxic-ischemic period. Seventy-three metabolites involved in various metabolic pathways such as glycolysis, tricarboxylic acid (TCA) cycle, nucleoside metabolism, lipid metabolism, oxidative stress and ionic homeostasis demonstrated significant changes. It is worth mentioning that we have detected neutral triglycerides (TGs) that are difficult to ionize and observed their accumulation in the ischemic region, which has been rarely reported in previous studies. The results not only help us discover biomarkers but also provide new insights into its mechanism for us to understand the pathological and physiological processes of the disease.