# The role of neuroactive kynurenine metabolites in the chronic sequelae of concussion and contact sport exposure

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $378,243

## Abstract

Project Summary/Abstract
There is an urgent need to characterize the long-term effects of contact sport exposure with and without prior
concussion, and to identify potential molecular mechanisms that may underlie these effects. An imbalance in
glutamatergic activity caused by neuroactive kynurenine pathway metabolites is one such mechanism behind
abnormalities of limbic system structure and function in a variety of disorders. The objective of this proposal is
to elucidate the relationship between neuroactive kynurenine pathway metabolites and chronic abnormalities in
the limbic system associated with repetitive concussion and head impact exposure from contact sport
participation. The central hypothesis is that prior concussion and/or exposure to contact sport lead to structural
and functional alterations in a limbic system centered on the rostral anterior cingulate cortex and hippocampus
resulting in sub-clinical mood-dysregulation, and that these changes are driven by neurotoxic kynurenine
pathway metabolites in the brain that are reflected by concentrations in blood. Male and female adults (age 18-
26) will be enrolled across three groups, including (1) contact sport athletes with a prior concussion, (2) contact
sport athletes with no prior concussion, and (3) non-contact sport athletes to separate the effects of contact
sport exposure with and without previous concussion. An advanced neuroimaging battery, a clinical battery,
and blood specimen will be collected in a single visit to address the following aims: (Aim 1) Test the hypothesis
that concussion and contact sport exposure are associated with structural differences in the limbic system that
correlate with neuroactive KP metabolites, and (Aim 2) Test the hypothesis that concussion and contact sport
exposure are associated with differences in limbic system functional connectivity and behavior that correlate
with neuroactive KP metabolites. We expect that this work will delineate the potential role of neuroactive KP
metabolites in the neurobiobehavioral sequelae of concussion and contact sport exposure for the millions of
athletes currently participating in contact sport. This information is of major public health significance because
it will stimulate bidirectional translational research that will ultimately lead to the development of
pharmaceutical treatments to prevent or reverse these effects in at-risk contact sport athletes. This hypothesis-
driven proposal is scientifically innovative because it will study the relationship between the long-term effects of
concussion/head impact exposure and one molecular pathway implicated in limbic system dysregulation in
parallel neuroscience research.
!

## Key facts

- **NIH application ID:** 9828119
- **Project number:** 5R01NS102225-03
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Timothy B. Meier
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,243
- **Award type:** 5
- **Project period:** 2017-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828119

## Citation

> US National Institutes of Health, RePORTER application 9828119, The role of neuroactive kynurenine metabolites in the chronic sequelae of concussion and contact sport exposure (5R01NS102225-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9828119. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*