摘要：SummaryResearch suggests contact sports affect neurological health. This study used permutation-based mediation statistics to integrate measures of metabolomics, neuroinflammatory miRNAs, and virtual reality (VR)-based motor control to investigate multi-scale relationships across a season of collegiate American football. Fourteen significant mediations (six pre-season, eight across-season) were observed where metabolitesalwaysmediated the statistical relationship between miRNAs and VR-based motor control (pSobelperm≤0.05; total effect>50%), suggesting a hypothesis that metabolites sit in the statistical pathway between transcriptome and behavior. Three results further supported a model of chronic neuroinflammation, consistent with mitochondrial dysfunction: (1) Mediating metabolites were consistently medium-to-long chain fatty acids, (2) tricarboxylic acid cycle metabolites decreased across-season, and (3) accumulated head acceleration events statistically moderated pre-season metabolite levels to directionally model post-season metabolite levels. These preliminary findings implicate potential mitochondrial dysfunction and highlight probable peripheral blood biomarkers underlying repetitive head impacts in otherwise healthy collegiate football athletes.Graphical abstractDisplay OmittedHighlights•Permutation-based mediation statistics can be applied to multi-scale biology problems•Fatty acids were a critical link between elevated miRNAs and motor control•HAEs interacted with pre-season metabolite levels to model post-season levels•Together, our observations point to brain-related mitochondrial dysfunctionTrauma; Metabolomics; Transcriptomics; Computer graphics
