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Smaller Dentate Gyrus and CA2 and CA3 Volumes Are Associated with Kynurenine Metabolites in Collegiate Football Athletes. J Neurotrauma 2016 07 15;33(14):1349-57



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2-s2.0-84977120369   11 Citations


An imbalance in kynurenine pathway metabolism is hypothesized to be associated with dysregulated glutamatergic neurotransmission, which has been proposed as a mechanism underlying the hippocampal volume loss observed in a variety of neurological disorders. Pre-clinical models suggest that the CA2-3 and dentate gyrus hippocampal subfields are particularly susceptible to excitotoxicity after experimental traumatic brain injury. We tested the hypothesis that smaller hippocampal volumes in collegiate football athletes with (n = 25) and without (n = 24) a concussion history would be most evident in the dentate gyrus and CA2-3 subfields relative to nonfootball healthy controls (n = 27). Further, we investigated whether the concentration of peripheral levels of kynurenine metabolites are altered in football athletes. Football athletes with and without a self-reported concussion history had smaller dentate gyrus (p < 0.05, p < 0.10) and CA2-3 volumes (p's < 0.05) relative to healthy controls. Football athletes with and without a concussion history had a trend toward lower (p < 0.10) and significantly lower (p < 0.05) kynurenine levels compared with healthy controls, while athletes with a concussion history had greater levels of quinolinic acid compared with athletes without a concussion history (p < 0.05). Finally, plasma levels of 3-hydroxykynurenine inversely correlated with bilateral hippocampal volumes in football athletes with a concussion history (p < 0.01), and left hippocampal volume was correlated with the ratio of kynurenic acid to quinolinic acid in football athletes without a concussion history (p < 0.05). Our results raise the possibility that abnormalities of the kynurenine metabolic pathway constitute a mechanism for hippocampal volume differences in the context of sports-related brain injury.

Author List

Meier TB, Savitz J, Singh R, Teague TK, Bellgowan PS


Timothy B. Meier PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Athletic Injuries
Brain Concussion
CA2 Region, Hippocampal
CA3 Region, Hippocampal
Dentate Gyrus
Magnetic Resonance Imaging
Quinolinic Acid
Young Adult
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75