Glial cell‐Derived, but Not Neuron‐Derived, Extracellular Vesicles May Serve as Novel Biomarkers of Acute Sport‐Related Concussion

Abstract

Extracellular vesicles (EVs) are released by cells of the central nervous system as a result of injury, including sport‐related concussion (SRC). Neurons, astrocytes, and oligodendrocytes have been shown to release EVs following brain injury and during pathological processes. The OBJECTIVE of this study was to evaluate circulating glial cell‐derived and neuronal‐derived EVs as novel biomarkers for acute SRC.METHODSCirculating EVs containing astrocyte‐specific glial fibrillary acidic protein (GFAP+EV), oligodendrocyte‐specific myelin oligodendrocyte glycoprotein (MOG+EV), and neuron specific enolase (NSE+EV) were analyzed in contact‐sport athletes with or without SRC (18‐29 yo, Control: n = 10, SRC: n = 7). Sodium citrate‐treated blood samples were obtained from athletes with SRC within 48‐hours of injury and from control athletes free of SRC for more than one year. Samples were double‐centrifuged to obtain platelet‐poor plasma and stored at ‐80°C until analyzed. Quantification of EVs was performed using a spectral flow cytometer. The study was approved by Temple University’s IRB, and all athletes provided written informed consent. Shapiro‐Wilk tests were used to determine if concentrations were normally distributed. Independent t‐tests were used to compare group means if samples showed normal distribution. Mann‐Whitney U tests were conducted if samples were not normally distributed. For correlational analysis, Pearson’s correlational coefficient was used for samples with normal distribution, while Spearman’s rank was used for nonnormally distributed samples. The Eta coefficient was used to assess correlations between gender and EV concentrations.RESULTSWe found that plasma concentrations of GFAP+EVs and MOG+EVs were significantly elevated in athletes with SRC within 48 hours of injury (GFAP+EVs t‐test: t = 5.77, p < 0.0001; MOG+EVs Mann‐Whitney U = 2.00, p = 0.0004) compared to athlete controls. Plasma concentrations of NSE+EVs were not significantly different between athletes with acute SRC and athlete controls (t‐test: t = 0.20, p = 0.85). None of the EV concentrations were significantly correlated with history of prior SRC, age, or gender.CONCLUSION. Glial cell‐derived EV concentrations were significantly higher among athletes with acute SRC compared to controls, while neuron‐derived EVs did not differ. Our results suggest that analysis of brain cell‐specific EVs may shed new light on a way to leverage EV‐based biomarker discovery for SRC.