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

Abstract

IntroductionIn 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.MethodsEight (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.ResultsFor 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.DiscussionOur 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.

Neuroinflammation drives sex-dependent effects on pain and negative affect in a murine model of repeated mild traumatic brain injury

“… 28 PET imaging of athletes with concussion also showed an increase in neuroinflammation in the striatum, where microglial activation persisted beyond clinical recovery. 50 Our study is consistent with these previous studies, but to our knowledge, this is the first report that rmTBI in adult mice induces neuroinflammation in the NAc that likely contributes to the negative affective state and pain hypersensitivity.…”

Neurological Effects of Repeated Blast Exposure in Special Operations Personnel

“… 18 Similarly, the TSPO ligand [ 18 F]DPA-714 was recently used to study microglial activation in collegiate athletes following a sports concussion, compared with healthy, age-matched controls. 19 That study demonstrated persistent elevated neuroinflammation in collegiate athletes who were diagnosed with a sport concussion and cleared for unrestricted return to play based on a clinical recovery. Using the TSPO ligand [ 11 C]PK11195, a recent study showed increased neuroinflammation in the hippocampus of athletes with sports-related concussion.…”

NHE1 Protein in Repetitive Mild TBI-Mediated Neuroinflammation and Neurological Function Impairment

“…Neuroinflammation and activation of reactive astrocytes and microglia are the pathological hallmarks in concussion TBI models [55,56]. Activation of oxidative stress and proinflammatory signaling pathways, such as nuclear factor κ-light chain-enhancer (NF-κB) and mitogen-activated protein kinase (MAPK), have been reported to play a role in these events [57,58].…”