Benjamin L Brett1, Jonathan Savitz2, Morgan Nitta3, Lezlie España4, T Kent Teague5, Lindsay D Nelson1, Michael A McCrea1, Timothy B Meier6. 1. Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, United States. 2. Laureate Institute for Brain Research, Tulsa, OK, United States; Oxley College of Health Sciences, Tulsa, OK, United States. 3. Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Psychology, Marquette University, Milwaukee, WI, United States. 4. Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States. 5. Departments of Surgery and Psychiatry, The University of Oklahoma, School of Community Medicine, United States; Department of Pharmaceutical Sciences, University of Oklahoma College of Pharmacy, United States. 6. Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, United States. Electronic address: tmeier@mcw.edu.
Abstract
BACKGROUND: There is a need to determine why prior concussion has been associated with adverse outcomes in some retired and active athletes. We examined whether serum inflammatory markers moderate the associations of prior concussion with hippocampal volumes and neurobehavioral functioning in active high school and collegiate athletes. METHODS: Athletes (N = 201) completed pre-season clinical testing and serum collection (C-reactive protein [CRP]; Interleukin-6 [IL]-6; IL-1 receptor antagonist [RA]) and in-season neuroimaging. Linear mixed-effects models examined associations of prior concussion with inflammatory markers, self-reported symptoms, neurocognitive function, and hippocampal volumes. Models examined whether inflammatory markers moderated associations of concussion history and hippocampal volume and/or clinical measures. RESULTS: Concussion history was significantly associated with higher symptom severity, p = 0.012, but not hippocampal volume or inflammatory markers (ps > 0.05). A significant interaction of prior concussion and CRP was observed for hippocampal volume, p = 0.006. Follow-up analyses showed that at high levels of CRP, athletes with two or more prior concussions had smaller hippocampal volume compared to athletes without prior concussion, p = 0.008. There was a significant interaction between prior concussion and levels of IL-1RA on memory scores, p = 0.044, i.e., at low levels of IL-1RA, athletes with two or more concussions had worse memory performance than those without prior concussion (p = 0.014). CONCLUSION: Findings suggest that certain markers of systemic inflammation moderate the association between prior concussion and hippocampal volume and episodic memory performance. Current findings highlight potential markers for predicting at-risk individuals and identify therapeutic targets for mitigating the long-term adverse consequences of cumulative concussion.
BACKGROUND: There is a need to determine why prior concussion has been associated with adverse outcomes in some retired and active athletes. We examined whether serum inflammatory markers moderate the associations of prior concussion with hippocampal volumes and neurobehavioral functioning in active high school and collegiate athletes. METHODS: Athletes (N = 201) completed pre-season clinical testing and serum collection (C-reactive protein [CRP]; Interleukin-6 [IL]-6; IL-1 receptor antagonist [RA]) and in-season neuroimaging. Linear mixed-effects models examined associations of prior concussion with inflammatory markers, self-reported symptoms, neurocognitive function, and hippocampal volumes. Models examined whether inflammatory markers moderated associations of concussion history and hippocampal volume and/or clinical measures. RESULTS: Concussion history was significantly associated with higher symptom severity, p = 0.012, but not hippocampal volume or inflammatory markers (ps > 0.05). A significant interaction of prior concussion and CRP was observed for hippocampal volume, p = 0.006. Follow-up analyses showed that at high levels of CRP, athletes with two or more prior concussions had smaller hippocampal volume compared to athletes without prior concussion, p = 0.008. There was a significant interaction between prior concussion and levels of IL-1RA on memory scores, p = 0.044, i.e., at low levels of IL-1RA, athletes with two or more concussions had worse memory performance than those without prior concussion (p = 0.014). CONCLUSION: Findings suggest that certain markers of systemic inflammation moderate the association between prior concussion and hippocampal volume and episodic memory performance. Current findings highlight potential markers for predicting at-risk individuals and identify therapeutic targets for mitigating the long-term adverse consequences of cumulative concussion.
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