Analysis of Energy Metabolism and Lipid Spatial Distribution in Hypoxic-Ischemic Encephalopathy Revealed by MALDI-MSI

作者：Xingxing Zhao, Peipei Chen, Yu Lun, Chuchu Gao, Sannan Wang, Zuming Yang, Zongtai Feng · 发表于：Biomedicines · 年份：2025 · DOI：10.3390/biomedicines13061431 · 被引用次数：6 · 研究领域：Metabolomics and Mass Spectrometry Studies、Mitochondrial Function and Pathology、Metabolism and Genetic Disorders

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal death and neurodevelopmental disorders, and its pathological mechanisms are closely related to disturbed energy metabolism and lipid remodeling. Exploring the spatial heterogeneity of metabolomics is essential to analyze the pathological process of HIE. Methods: In this study, we established a neonatal mouse hypoxic-ischemic brain damage (HIBD) model by the modified Rice method, and analyzed various metabolic pathways such as the tricarboxylic acid (TCA) cycle, purine metabolism, and lipid metabolism in the ischemic edema area, with contralateral and control brain tissues using matrix-assisted laser desorption mass spectrometry imaging (MALDI-MSI) with a spatial resolution of 50 μm. Results: In the HIBD model, key metabolites of the tricarboxylic acid (TCA) cycle (citrate, succinate, L-glutamate, glucose, aspartate, and glutamine) were significantly enriched in the edematous area compared with the control (fold change: 1.52–2.82), which suggests a blockage of mitochondrial function; ATP/ADP/AMP levels were reduced by 53–73% in the edematous area, and xanthine was abnormally accumulated in the hippocampus of the affected side, suggesting energy depletion and altered purine metabolism; lipid remodeling showed regional specificity: some unsaturated fatty acids, such as docosahexaenoic acid, were abnormally accumulated in the hippocampus. In contrast, pentadecanoic acid levels were reduced acr...