Recent Advances in Blood-Based Biomarkers of Remote Combat-Related Traumatic Brain Injury
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(2020) 20:54
NEUROTRAUMA (D. SANDSMARK, SECTION EDITOR)
Recent Advances in Blood-Based Biomarkers of Remote Combat-Related Traumatic Brain Injury Sara M. Lippa 1 & J. Kent Werner 2,3,4 & Matthew C. Miller 2 & Jessica M. Gill 4,5 & Ramon Diaz-Arrastia 6 & Kimbra Kenney 1,2 Accepted: 17 September 2020 # This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2020
Abstract Purpose of Review Traumatic brain injury (TBI) is highly prevalent among service members and Veterans (SMVs) and associated with changes in blood-based biomarkers. This manuscript reviews candidate biomarkers months/years following militaryassociated TBI. Recent Findings Several blood-based biomarkers have been investigated for diagnostic or prognostic use to inform care years after military-associated TBI. The most promising include increased levels of plasma/serum and exosomal proteins reflecting neuronal, axonal and/or vascular injury, and inflammation, as well as altered microRNA expression and auto-antibodies of central nervous system markers. Summary Diagnostic and prognostic biomarkers of remote TBI outcomes remain in the discovery phase. Current evidence does not yet support single or combination biomarkers for clinical diagnostic use remotely after injury, but there are promising candidates that require validation in larger, longitudinal studies. The use of prognostic biomarkers of future neurodegeneration, however, holds much promise and could improve treatments and/or preventive measures for serious TBI outcomes. Keywords Traumatic brain injury . Concussion . Biomarker . Exosome . Military . miRNA
Introduction Traumatic brain injury (TBI) is a common consequence of warfare and military service. During Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn, more than 400,000 TBIs were diagnosed since 2000 [1]. The large majority of TBIs sustained in both military and
This article is part of the Topical Collection on Neurotrauma * Kimbra Kenney [email protected] 1
National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD, USA
2
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
3
Sleep Medicine, WRNMMC, Bethesda, MD, USA
4
CNRM, USUHS, Bethesda, MD, USA
5
Brain Tissue Injury, NINR, NIH, Bethesda, MD, USA
6
Department of Neurology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
civilian contexts are mild [1, 2], a type of injury that was also common but ignored in prior conflicts [3, 4]. In military and veteran populations, patients with mTBI often first present for treatment months or years following their injury. In these cases, diagnosis may be reliant on self-report. Identifying biomarkers that could objectively detect mild TBI (mTBI) several months after injury would aid diagnosis, especially as mTBI is rarely associated with abnormal neuroimaging [5]. Although complete recovery from TBI most often occurs within month
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