Common lipidomic signatures across distinct acute brain injuries in patient outcome prediction
: Hellström, Santtu; Sajanti, Antti; Srinath, Abhinav; Bennett, Carolyn; Girard, Romuald; Jhaveri, Aditya; Cao, Ying; Falter, Johannes; Frantzén, Janek; Koskimäki, Fredrika; Lyne, Seán B.; Rantamäki, Tomi; Takala, Riikka; Posti, Jussi P.; Roine, Susanna; Kolehmainen, Sulo; Nazir, Kenneth; Jänkälä, Miro; Puolitaival, Jukka; Rahi, Melissa; Rinne, Jaakko; Nieminen, Anni I.; Castrén, Eero; Koskimäki, Janne
Publisher: Elsevier
: SAN DIEGO
: 2025
: Neurobiology of Disease
: Neurobiology of Disease
: NEUROBIOL DIS
: 106762
: 204
: 12
: 0969-9961
: 1095-953X
DOI: https://doi.org/10.1016/j.nbd.2024.106762
: https://doi.org/10.1016/j.nbd.2024.106762
: https://research.utu.fi/converis/portal/detail/Publication/477998786
Lipidomic alterations have been associated with various neurological diseases. Examining temporal changes in serum lipidomic profiles, irrespective of injury type, reveals promising prognostic indicators. In this longitudinal prospective observational study, serum samples were collected early (46 +/- 24 h) and late (142 +/- 52 h) post- injury from 70 patients with ischemic stroke, aneurysmal subarachnoid hemorrhage, and traumatic brain injury that had outcomes dichotomized as favorable (modified Rankin Scores (mRS) 0-3) and unfavorable (mRS 4-6) three months post-injury. Lipidomic profiling of 1153 lipids, analyzed using statistical and machine learning methods, identified 153 lipids with late-stage significant outcome differences. Supervised machine learning pinpointed 12 key lipids, forming a combinatory prognostic equation with high discriminatory power (AUC 94.7 %, sensitivity 89 %, specificity 92 %; p < 0.0001). Enriched functions of the identified lipids were related to sphingolipid signaling, glycerophospholipid metabolism, and necroptosis (p < 0.05, FDR-corrected). The study underscores the dynamic nature of lipidomic profiles in acute brain injuries, emphasizing late-stage distinctions and proposing lipids as significant prognostic markers, transcending injury types. These findings advocate further exploration of lipidomic changes for a comprehensive understanding of pathobiological roles and enhanced prediction for recovery trajectories.
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Funding for this work was provided to JK by the Sigrid Juselius Foundation and the Finnish Medical Foundation. AS received support from both the Sigrid Juselius Foundation and the Maire Taponen Foundation, while SH was funded by the Sigrid Juselius Foundation. JPP is funded by the Academy of Finland (grant #17379) and the Maire Taponen Foundation.
