장현준 (기초과학연구원)

이보영 (기초과학연구원)

이창준 (기초과학연구원)

장현준 (기초과학연구원)

이재훈 (기초과학연구원)

이보영 (기초과학연구원)

이창준 (기초과학연구원)

Stroke is a major neurological disorder caused by vascular damage in the central nervous system (CNS), leading to high mortality and disability rates worldwide. Ischemic stroke, the most common subtype, results from arterial occlusion that reduces or blocks blood flow to brain tissue. This condition induces the formation of fibrotic cores and glial barriers, structures regulated by extracellular matrix (ECM) glycoproteins, including collagen. Although previous studies have linked changes in glycosylation and amino acid metabolism to ischemic stroke, the spatial distribution of N-glycans and amino acids in the post-stroke brain remains poorly understood. In this study, we employed MALDI mass spectrometry imaging to visualize and quantify region-specific alterations in N-glycans and amino acids in a photothrombosis-induced ischemic stroke model. Our results showed that N-glycans with no or only one fucose residue were significantly increased in the fibrotic core, whereas N-glycans with two or more fucose residues were significantly decreased. These N-glycan changes were reversible by two different treatments that reduced both the fibrotic core and glial barrier size. Importantly, astrocyte-specific knockdown of Fut8—an enzyme critical for core fucosylation—significantly reduced fibrotic scar formation, suggesting that astrocytic N-glycosylation plays a pivotal role in post-stroke fibrotic remodeling. In a non-human primate model, we also identified significant changes in fucosylated N-glycans in the fibrotic core and glial penumbra following ischemic stroke. Additionally, we observed dynamic alterations in amino acid levels within the fibrotic core and glial barrier. Collectively, our findings underscore the importance of astrocyte-specific N-glycosylation and amino acid alterations in stroke pathology, and highlight novel molecular targets for therapeutic intervention.

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