Shared metabolomic signatures for prognostic precision across brain injuries

Abstract

<h3>Introduction</h3><p>Metabolomic alterations have been linked to a range of neurological conditions. Investigating temporal changes in serum metabolomic profiles, regardless of the type of brain injury may reveal prognostic indicators.</p><h3>Research question</h3><p>We hypothesize that specific metabolomic signatures, conserved across different acute brain injuries, can serve as robust predictors of patient outcomes.</p><h3>Material and methods</h3><p>In this longitudinal prospective observational study, serum samples were collected early (2 ± 1 day) and late (6 ± 2 days) post-injury from a total of 73 patients with ischemic stroke (n = 30), aneurysmal subarachnoid hemorrhage (n = 30), and traumatic brain injury (n = 13). Outcomes were categorized as favorable (modified Rankin Scores (mRS) 0–3) and unfavorable (mRS 4–6) three months post-injury. Metabolomic profiling (Orbitrap mass spectrometry) of 462 metabolites, analyzed using statistical and machine learning methods, identified significant outcome differences (p < 0.05, FDR-corrected).</p><h3>Results</h3><p>Early-stage samples indicated good prognostic power with a combination of uridine, tryptophan, and lactic acid (AUC 88.8 %, OR 5.29, p < 0.0001). Late-stage samples showed high discriminatory accuracy with a combination of prostaglandin J2, gamma-linolenic acid, N-acetyl-L-alanine, uridine, N-alpha-acetyl-L-asparagine, 3-hydroxy-3-methylglutarate, propionate, and creatinine (AUC 94.4 %, OR 14.5, p < 0.0001). Pathway analyses revealed significant associations with glycolysis/gluconeogenesis, pyrimidine metabolism, and tryptophan metabolism at early stages, and fatty acid biosynthesis, pyruvate metabolism, phenylalanine metabolism, and tryptophan metabolism at later stages.</p><h3>Discussion and conclusion</h3><p>These findings underscore the dynamic nature of metabolomic profiles in acute brain injuries and highlight common metabolites as significant prognostic markers across brain injury types.</p>