# Molecular imaging of brain injury and repair in NFL players

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $584,802

## Abstract

PROJECT SUMMARY
The goal of this project is to understand the contribution of persistent immune signaling to brain injury and
repair in former National Football League (NFL) players through imaging and the study of circulating cytokines.
We are concerned that such individuals develop cognitive impairment at a higher rate than the general
population, which may be generalizable to those participating in other sports or with other forms of repeated
traumatic brain injury (TBI). We focus on measuring the activity of microglia, the resident immune cells of the
CNS, because of their importance in responding to brain injury. Based on published evidence and our
preliminary data, we hypothesize that former NFL players have functionally hyper-activated microglia located
in brain regions vulnerable to injury from collision sports. Such injury is marked by increased expression of
translocator protein 18 KDa (TSPO) by microglial cells and reactive astrocytes. We further hypothesize that
prolonged microglial activation in regions of repeated axonal injury causes neuronal energy and functional
deficits that are mechanistically linked to neurodegeneration. We recently showed that [11C]DPA-713 (DPA)
positron emission tomography (PET) can be used to measure increased expression of TSPO, a marker of
brain injury and repair, in human neurodegenerative disease. In the first study of TSPO in NFL players, we
found higher DPA binding in the brains of elderly players compared to elderly controls. Our newer published
findings also reveal higher DPA binding in a cohort of young, active or recently retired NFL players compared
to a control group of non-collision sport athletes in several of the same cortical and mesial temporal lobe
structures tested in the published pilot of older players. Two young players recently returned for two-year
follow-up imaging that revealed stable TSPO distribution in all brain regions tested, and one of them also
showed PET-based evidence of increased tau burden in several brain regions at this second visit. He was
among eight of 15 young NFL players with high peripheral pro-inflammatory marker profile at his baseline DPA
imaging, supporting the hypothesized link between pro-inflammatory signaling and vulnerability to aberrant tau
deposition after repeated TBI. We now propose to measure the distribution of TSPO using DPA PET in the
brains of 35 recently former NFL players compared to a control group of 35 healthy, non-collision sport athletes
(Aim 1) in parallel with biofluid (CSF, plasma) assays for markers of inflammation in the same population (Aim
2). The (two-year) persistence of these immune markers will be tested in Aim 3. Our design uses DPA, which
has advantages over other 2nd-generation radiotracers for imaging TSPO. Our infrastructure for research of
carefully selected young, former NFL players and controls is unique and yet aligns with methodology of other
groups studying elderly NFL players. By characterizing the persistent inflam...

## Key facts

- **NIH application ID:** 9825398
- **Project number:** 5R01NS100847-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jennifer Marie Coughlin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $584,802
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9825398

## Citation

> US National Institutes of Health, RePORTER application 9825398, Molecular imaging of brain injury and repair in NFL players (5R01NS100847-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9825398. Licensed CC0.

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