ArticleFrontiers in neurology2026
Ferroptosis-associated candidate genes in aneurysmal subarachnoid hemorrhage: evidence from human peripheral blood and mouse brain.
Article in Frontiers in neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Aneurysmal subarachnoid hemorrhage (aSAH) has high morbidity and mortality. Ferroptosis may contribute to aSAH-related brain injury, but its peripheral and brain-associated signatures remain unclear. Methods: Human peripheral-blood dataset GSE36791 (43 aSAH, 18 controls) was analyzed using limma, FerrDb intersection, WGCNA, GO/KEGG enrichment, and PPI-based prioritization. qPCR validation was performed in peripheral blood from 10 aSAH patients and 10 non-SAH controls; aSAH samples were collected within 24 h after rupture. Mean ages were 60.2 ± 7.7 and 63.6 ± 8.9 years, with 5 and 4 males, respectively. Brain-level validation used GSE79416 mouse cortex and OMIX006611 mouse SAH single-cell RNA-seq data. Male C57BL/6 J mice (8 weeks, 20-22 g) underwent cisterna magna autologous blood injection; brain tissues were collected 1 day after SAH (n = 6/group). Immune infiltration and molecular docking were also performed. Results: Among 2,645 DEGs, 35 were ferroptosis-related. MAPK3, STAT3, G6PD, and PGD were prioritized as ferroptosis-associated candidate genes and were upregulated in human aSAH peripheral blood, mouse SAH cortex, and the clinical qPCR cohort. Single-cell analysis showed expression of the corresponding mouse genes across annotated brain cell types, especially immune/glial populations. In mouse SAH brain tissue, MAPK3/ERK1, STAT3, PGD, and G6PD protein levels increased, p-STAT3/STAT3 ratio was elevated, MDA content increased, and GPX4 activity decreased. Immune profiling showed increased neutrophils, mast cells, and activated dendritic cells. Ganoderic acid A was prioritized as a preliminary in silico candidate. Conclusion: MAPK3, STAT3, G6PD, and PGD are ferroptosis-associated candidate genes in aSAH, supported by human peripheral-blood, mouse cortex, single-cell, and mouse brain validation. Ganoderic acid A remains an exploratory in silico candidate requiring further functional validation.
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