Lipidomic Comparison of Detergent-Soluble and Detergent-Resistant Lipid Domains Isolated From Rat Cerebellum and the Effect of Hypoxia–Ischemia Using UPLC-HDMSE

Sep 29, 2026

Hypoxic ischemic encephalopathy (HIE) caused by insufficient oxygen or blood flow to the brain can trigger inflammation, disrupt neurodevelopment, and even lead to death. Microdomain lipid remodeling may affect key regulatory processes, yet post-HIE changes in membrane lipid composition remain incompletely characterized. This study applies untargeted lipidomics to examine hypoxia–ischemia effects on detergent-resistant (DRM) and detergent-soluble (DSM) membrane domains from rat cerebellum. UPLC-HDMSE enables profiling of DRM-specific lipid alterations.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

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Introduction

Hypoxic–ischemic encephalopathy and lipid microdomains

Detergent-resistant vs detergent-soluble membrane domains

Lipid rafts, subcellular localization, and lipidomics

Journal of Mass Spectrometry RESEARCH ARTICLE OPEN ACCESS Lipidomic Comparison of Detergent-Soluble and Detergent-Resistant Lipid Domains Isolated From Rat Cerebellum and the Effect of Hypoxia–Ischemia Using UPLC-HDMSE Samuel A. Krug1 | Min He2 | Ningfeng Tang2 | Cynthia Bearer2 | Maureen A. Kane1 1Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland, USA | 2Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA Correspondence: Maureen A. Kane ([mkane@rx.umaryland.edu](mkane@rx.umaryland.edu)) Received: 8 May 2025 | Revised: 30 October 2025 | Accepted: 6 November 2025 Keywords: hypoxic ischemia | lipid membrane | lipidomics | liquid chromatography–tandem mass spectrometry | membrane domains ABSTRACT Hypoxic ischemic encephalopathy (HIE) due to insufficient oxygen or blood flow to the brain can result in inflammation, impaired neurodevelopment, or death. Changes to microdomain lipid composition may contribute to altered structure and function of key regulatory processes; however, knowledge regarding changes to membrane lipid composition after HIE is incomplete. Here, we describe the application of untargeted lipidomics to investigate the impact of hypoxia–ischemia on detergent-resistant membrane (DRM) and detergent-soluble membrane (DSM) domains fractionated from the cerebellum in a rat model of HIE. Lipidomics utilized ultra performance liquid chromatography coupled to data independent tandem mass spectrometry with traveling wave ion mobility. Lipid alterations specific to the DRM domains after hypoxia–ischemia included lysophospholipids, sphingomyelins, ceramides, triglycerides, and phosphatidylethanolamines, which are lipid species that have been linked to cognitive and neuronal impairment. The advances in lipidomics have enabled the tools available to study lipid composition. These data may provide insight into membrane disruption after HIE in relation to lipid composition and concentration. 1 | Introduction Hypoxic–ischemic encephalopathy (HIE) due to insufficient oxygen or blood flow to the brain can result in inflammation, impaired neurodevelopment, or death [1]. HIE is a perinatal insult that changes the protein distribution in organized lipid microdomains in the developing cerebellum [2]. One such protein, L1, is a cell adhesion protein of the immunoglobulin superfamily associated with lipid rafts in the cerebellum during specific phases of brain development [3, 4] . L1 mediates neurite elongation and migration of neuronal precursors; this function is dependent on its association with lipid raft domains [5–8]. A variety of perinatal insults can change the L1 distribution to lipid rafts disrupting cerebellar development including HIE, ethanol exposure, toluene exposure, and bilirubin excess [1, 4, 9, 10] . Molecules like choline, crucial for structural components of cells, have been shown to mitigate ethanol-induced disruption of lipid rafts [8] . Choline-containing phospholipids are a component of lipid rafts in cell membranes, including phosphatidylcholine and sphingomyelin. As such, changes to the composition of ordered lipid domains may be central to the disruption of lipid raft–mediated signaling in the developing cerebellum. Lipid raft formation is driven by lipid–lipid interactions that influence the size and lipid composition of the domain [9] . The microdomains within membranes can be isolated into two distinct fractions. Ordered lipid domains are detergent-resistant, and within this manuscript are termed detergent-resistant This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2026 The Author(s). Journal of Mass Spectrometry published by John Wiley & Sons Ltd. Journal of Mass Spectrometry, 2026; 61:e70000 1 of 10 [https://doi.org/10.1002/j

FAQs

What is the study investigating in the rat cerebellum model?

The study examines how hypoxia–ischemia affects lipid composition in detergent-resistant membrane (DRM) and detergent-soluble membrane (DSM) domains using untargeted lipidomics.

Why are DRM and DSM important for understanding membrane organization?

DRM and DSM represent membrane fractions with different properties; DRM domains are less flexible and less permeable and are enriched in lipids such as saturated lipids, sterols, sphingolipids, and triglycerides.

Which analytical approach is used to profile lipids in this work?

Lipids are profiled with ultra performance liquid chromatography coupled to data independent tandem mass spectrometry with traveling wave ion mobility (UPLC-HDMSE).

Sep 29, 2026

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