학술논문
A Pilot Study Investigating the Use of Serum Glial Fibrillary Acidic Protein to Monitor Changes in Brain White Matter Integrity After Repetitive Head Hits During a Single Collegiate Football Game.
Document Type
Academic Journal
Author
Bazarian JJ; Department of Emergency Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.; Abar B; Department of Emergency Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.; Merchant-Borna K; Department of Emergency Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.; Pham DL; Center for Neuroscience and Regenerative Medicine, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.; Rozen E; Department of Athletics and Recreation, University of Rochester, Rochester, New York, USA.; Mannix R; Departments of Pediatrics and Emergency Medicine, Harvard Medical School, Boston, Massachusetts, USA.; Kawata K; Department of Kinesiology, Indiana University, Bloomington, Indiana, USA.; Chou Y; Center for Neuroscience and Regenerative Medicine, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.; Stephen S; University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.; Gill JM; Johns Hopkins School of Nursing and Medicine, Baltimore, Maryland, USA.
Source
Publisher: Mary Ann Liebert Country of Publication: United States NLM ID: 8811626 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-9042 (Electronic) Linking ISSN: 08977151 NLM ISO Abbreviation: J Neurotrauma Subsets: MEDLINE
Subject
Language
English
Abstract
Repetitive head hits (RHHs) in sports and military settings are increasingly recognized as a risk factor for adverse neurological outcomes, but they are not currently tracked. Blood-based biomarkers of concussion have recently been shown to increase after nonconcussive RHHs during a single sporting contest, raising the possibility that they could be used in real time to monitor the brain's early response to repeated asymptomatic head hits. To test this hypothesis, we measured GFAP in serum immediately before (T0), immediately after (T1) and 45 min (T2) after a single collegiate football game in 30 athletes. Glial fibrillary acidic protein (GFAP) changes were correlated with three measures of head impact exposure (number of hits, total linear acceleration, and total rotational acceleration captured by helmet impact sensors) and to changes in brain white matter (WM) integrity, estimated by regional changes in fractional anisotropy (FA) and mean diffusivity (MD) on diffusion tensor imaging from 24 h before (T1) to 48 h after (T3) the game. To account for the potentially confounding effects of physical exertion on GFAP, correlations were adjusted for kilocalories of energy expended during the game measured by wearable body sensors. All 30 participants were male with a mean age of 19.5 ± 1.2 years. No participant had a concussion during the index game. We observed a significant increase in GFAP from T0 to T1 (mean 79.69 vs. 91.95 pg/mL, p = 0.008) and from T0 to T2 (mean 79.69 vs. 99.21 pg/mL, p < 0.001). WM integrity decreased in multiple WM regions but was statistically significant in the right fornix (mean % FA change -1.43, 95% confidence interval [CI]: -2.20, -0.66). T0 to T2 increases in GFAP correlated with reduced FA in the left fornix, right fornix, and right medical meniscus and with increased MD in the right fornix ( r -values ranged from 0.59 to 0.61). Adjustment for exertion had minimal effect on these correlations. GFAP changes did not correlate to head hit exposure, but after adjustment for exertion, T0 to T2 increases correlated with all three hit metrics ( r -values ranged from 0.69 to 0.74). Thus, acute elevations in GFAP after a single collegiate football game of RHHs correlated with in-game head hit exposure and with reduced WM integrity 2 days later. These results suggest that GFAP may be a biologically relevant indicator of the brain's early response to RHHs during a single sporting event. Developing tools to measure the neurological response to RHHs on an individual level has the potential to provide insight into the heterogeneity in adverse outcomes after RHH exposure and for developing effective and personalized countermeasures. Owing to the small sample size, these findings should be considered preliminary; validation in a larger, independent cohort is necessary.