  Recent research has shown there can be detrimental neurological effects of
short- and long-term exposure to contact sports. In the present study,
metabolomic profiling was combined with inflammatory miRNA quantification,
computational behavior with virtual reality (VR) testing of motor control, and
head collision event monitoring to explore trans-omic and collision effects on
human behavior across a season of players on a collegiate American football
team. We integrated permutation-based statistics with mediation analyses to
test complex, directional relationships between miRNAs, metabolites, and VR
task performance. Fourteen significant mediations (metabolite = mediator; miRNA
= independent variable; VR score = dependent variable) were discovered at
preseason (N=6) and across season (N=8) with Sobel p-values less than or equal
to 0.05 and with total effects at or exceeding 50%. The majority of mediation
findings involved long to medium chain fatty acids (2-HG, 8-HOA, UND, sebacate,
suberate, and heptanoate). In parallel, TCA metabolites were found to be
significantly decreased at postseason relative to preseason. HAEs were
associated with metabolomic measures and miRNA levels across-season. Together,
these observations suggest a state of chronic HAE-induced neuroinflammation (as
evidence by elevated miRNAs) and mitochondrial dysfunction (as observed by
abnormal FAs and TCA metabolites) that together produce subtle changes in
neurological function (as observed by impaired motor control behavior). These
findings point to a shift in mitochondrial metabolism, away from mitochondria
function, consistent with other illnesses classified as mitochondrial
disorders, suggesting a plausible mechanism underlying HAEs in contact sports
and potential avenue for treatment intervention.
