N-glycomics profiling reveals alteration of fucosylation in early acute ischemic stroke from mouse brain tissue to human serum

TL;DR

This study compares glycan changes in mouse brain tissue and human serum during early stroke, finding reduced fucosylation as a potential diagnostic marker.

Contribution

The first comprehensive cross-species glycomic analysis of early acute ischemic stroke, revealing conserved fucosylation alterations.

Findings

Identified 9 ischemia-sensitive glycans in mouse brain tissues and 6 serum biomarkers in humans.

Conserved downregulation of fucosylation was observed in both mouse and human samples.

Fucosylation deficiency correlates with dysregulated inflammatory responses and impaired cellular stress pathways.

Abstract

Accumulating evidence suggests that N-glycosylation plays a crucial role in modulating ischemic pathophysiology. However, the dynamic alterations of N-glycosylation patterns during the early phase of acute ischemic stroke (AIS) have not been systematically investigated.

We employed matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to profile the glycome of murine cerebral tissues and identify differentially expressed glycans and glycosylation features during early AIS progression. To validate these findings, we further analyzed serum glycome profiles from human AIS patients in the early disease stage. Comprehensive statistical analyses were conducted to identify potential glycome biomarkers.

Comprehensive glycomic profiling identified 42 distinct N-glycan structures in murine brain tissues and 31 in serum samples. Through integrated multivariate statistical analyses, we identified 9 ischemia-sensitive cerebral glycans and 6 serum biomarkers. While no individual glycan structures were conserved between species, we identified a conserved downregulation of fucosylation as a key feature (murine cohort AUC = 0.98; human cohort AUC = 0.78).

This study presents the first comprehensive comparison of glycomic profiles in early AIS from mouse brain tissue and human serum, identifying a conserved fucosylation deficiency as a potential class of diagnostic indicators for clinical detection and therapeutic targeting. The observed deficiency was correlated with a potential mechanistic link to dysregulated glycan-mediated inflammatory responses and impaired cellular stress response pathways.

The online version contains supplementary material available at 10.1186/s12014-025-09578-w.

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