Hyunhwa Lee, PhD, PMHNP-BC;
Kian Merchant-Borna, MPH;
Dan Wang, PhD.;
Viktoria Bogner MD;
Martijn van Griensven MD, PhD.;
Jessica Gill, RN, PhD.;
Jeffrey J. Bazarian, MD., MPH
University of Nevada, Las Vegas, School of Nursing, Las Vegas, NV, United States
Department of Emergency Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States
National Institute for Nursing Research, National Institutes of Health, Bethesda, MD, United States
Ludwig Maximilians University, Munich, Germany
Experimental Trauma Surgery, Department of Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
Peripheral blood transcriptome analysis may estimate changes in gene activities of the brain tissue, providing clues into the physiologic underpinnings of recovery from sports concussion. This study examined changes in peripheral blood mononuclear cell (PBMC) transcriptome expression following sports concussion prospectively.
Between 2010 and 2012, 253 contact athletes from two universities in Rochester, New York, underwent PBMC collection at the start of the sport season (baseline).
There were 16 athletes who subsequently developed a sports concussion and underwent repeat PBMC collection within 6 hours of injury (acutely) as well as at 7 days post-injury (sub-acutely). Controls were 16 non-concussed teammates and they underwent PBMC collection at the same time of within 6 hours of injury for concussed athletes. Using Affymetrix microarray, PBMC transcriptome expression at baseline was compared to ones acutely and sub-acutely post-concussion. Control PBMC samples were used to estimate the contribution of physical exertion to post-concussion gene changes. Ingenuity Pathway Analysis was used to translate differential gene expression into gene networks most likely affected by sports concussion. Clinical recovery was determined by examining changes in post-concussive symptoms, postural stability, and cognition from baseline to the sub-acute time point.
Concussed athletes had significant changes in transcriptome expression at both the acute and sub-acute time points compared to their baseline profiles. Acute transcriptional changes were centered on inflammatory activity with key transcriptional hubs being interleukins 6 and 12, toll-like receptor 4, and NF-ÎºB. Sub-acute gene expression changes were centered on glucocorticoid receptor signaling with NF-ÎºB, follicle stimulating hormone, chorionic gonadotropin, and protein kinase catalytic subunit being the key transcriptional hubs. We observed no significant changes in sub-acute post-concussive symptoms, postural stability, or cognition; all concussed athletes were recovered by the sub-acute time point. There were no significantly differential gene expressions due to changes of physical exertion change.
Acute post-concussion gene transcriptional changes reflect regulation of the innate immune response as well as the transition to an acquired, adaptive immune response. By 7 days post-injury, transcriptional activity is centered on the regulation of the hypothalamic-pituitary-adrenal axis. These findings illustrate a time-dependent shift in gene expression post-injury that may provide insight into the pathophysiology of recovery from sports concussion. Future efforts to compare these results to expressional changes among athletes who do not recover from sports concussion could suggest putative targets for therapeutic intervention.