Microglial activation persists beyond clinical recovery following sport concussion in collegiate athletes

Kiel D Neumann; Vikram Seshadri; Xavier D Thompson; Donna K Broshek; Jason Druzgal; James C Massey; Benjamin Newman; Jose Reyes; Spenser R Simpson; Katelyenn S McCauley; James Patrie; James R Stone; Bijoy K Kundu; Jacob E Resch

doi:10.3389/fneur.2023.1127708

Microglial activation persists beyond clinical recovery following sport concussion in collegiate athletes

Front Neurol. 2023 Mar 24:14:1127708. doi: 10.3389/fneur.2023.1127708. eCollection 2023.

Authors

Affiliations

¹ Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN, United States.
² Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, United States.
³ Department of Kinesiology, University of Virginia, Charlottesville, VA, United States.
⁴ Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, United States.
⁵ Department of Public Health Sciences, University of Virginia, Charlottesville, VA, United States.
⁶ Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States.

Abstract

Introduction: In concussion, clinical and physiological recovery are increasingly recognized as diverging definitions. This study investigated whether central microglial activation persisted in participants with concussion after receiving an unrestricted return-to-play (uRTP) designation using [¹⁸F]DPA-714 PET, an in vivo marker of microglia activation.

Methods: Eight (5 M, 3 F) current athletes with concussion (Group 1) and 10 (5 M, 5 F) healthy collegiate students (Group 2) were enrolled. Group 1 completed a pre-injury (Visit1) screen, follow-up Visit2 within 24 h of a concussion diagnosis, and Visit3 at the time of uRTP. Healthy participants only completed assessments at Visit2 and Visit3. At Visit2, all participants completed a multidimensional battery of tests followed by a blood draw to determine genotype and study inclusion. At Visit3, participants completed a clinical battery of tests, brain MRI, and brain PET; no imaging tests were performed outside of Visit3.

Results: For Group 1, significant differences were observed between Visits 1 and 2 (p < 0.05) in ImPACT, SCAT5 and SOT performance, but not between Visit1 and Visit3 for standard clinical measures (all p > 0.05), reflecting clinical recovery. Despite achieving clinical recovery, PET imaging at Visit3 revealed consistently higher [¹⁸F]DPA-714 tracer distribution volume (VT) of Group 1 compared to Group 2 in 10 brain regions (p < 0.001) analyzed from 164 regions of the whole brain, most notably within the limbic system, dorsal striatum, and medial temporal lobe. No notable differences were observed between clinical measures and VT between Group 1 and Group 2 at Visit3.

Discussion: Our study is the first to demonstrate persisting microglial activation in active collegiate athletes who were diagnosed with a sport concussion and cleared for uRTP based on a clinical recovery.

Keywords: molecular imaging; neuroinflammation; positron emission tomography; sport concussion; traumatic brain injury.

Abstract

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