Traumatic brain injuries (TBIs) are clinically grouped by severity: mild, moderate and severe. Mild TBI (the least severe form) is synonymous with concussion and is typically caused by blunt non-penetrating head trauma. The trauma causes stretching and tearing of axons, which leads to diffuse axonal injury — the best-studied pathogenetic mechanism of this disorder. However, mild TBI is defined on clinical grounds and no well-validated imaging or fluid biomarkers to determine the presence of neuronal damage in patients with mild TBI is available. Most patients with mild TBI will recover quickly, but others report persistent symptoms, called post-concussive syndrome, the underlying pathophysiology of which is largely unknown. Repeated concussive and subconcussive head injuries have been linked to the neurodegenerative condition chronic traumatic encephalopathy (CTE), which has been reported post-mortem in contact sports athletes and soldiers exposed to blasts. Insights from severe injuries and CTE plausibly shed light on the underlying cellular and molecular processes involved in mild TBI. MRI techniques and blood tests for axonal proteins to identify and grade axonal injury, in addition to PET for tau pathology, show promise as tools to explore CTE pathophysiology in longitudinal clinical studies, and might be developed into diagnostic tools for CTE. Given that CTE is attributed to repeated head trauma, prevention might be possible through rule changes by sports organizations and legislators.
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K.B. holds the Torsten Söderberg Professorship in Medicine at the Royal Swedish Academy of Sciences. P.M.K. is supported by the US Department of Defense (grant WH81XWH-14-2-0018). H.L. is supported by the US National Institute of Neurological Disorders and Stroke (grant R21 NS086714-01). A.M. is supported by the US Department of Veterans Affairs, the Veterans Affairs Biorepository (program CSP 501), the National Institute of Neurological Disorders and Stroke (grant 1U01NS086659-01), the US National Institute of Ageing Boston University Alzheimer disease Disease Center (grant P30AG13846; supplement 0572063345–5), the Department of Defense (W81XWH-13-2-0064, CENC award WXWH-13-2-0095 and VA I01 RX 002170) and the National Operating Committee on Standards for Athletic Equipment and the Concussion Legacy Foundation. This work was also supported by unrestricted gifts from the Andlinger Foundation, the World Wrestling Entertainment and the National Football League.
K.B. has served on advisory boards for IBL International and Roche Diagnostics and provided consultation to Fujirebio Europe. K.B. and H.Z. are cofounders of Brain Biomarker Solutions. P.M.K., D.L.B., H.L., A.M., G.M.R. and K.Y. declare no competing interests.
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