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Abstract
Objective To measure exosomal and plasma levels of candidate blood biomarkers in veterans with history of mild traumatic brain injury (mTBI) and test their relationship with chronic symptoms.
Methods Exosomal and plasma levels of neurofilament light (NfL) chain, tumor necrosis factor (TNF)–α, interleukin (IL)–6, IL-10, and vascular endothelial growth factor (VEGF) were measured using an ultrasensitive assay in a cohort of 195 veterans, enrolled in the Chronic Effects of Neurotrauma Consortium Longitudinal Study. We examined relationships between candidate biomarkers and symptoms of postconcussive syndrome (PCS), posttraumatic stress disorder (PTSD), and depression. Biomarker levels were compared among those with no traumatic brain injury (TBI) (controls), 1–2 mTBIs, and repetitive (3 or more) mTBIs.
Results Elevated exosomal and plasma levels of NfL were associated with repetitive mTBIs and with chronic PCS, PTSD, and depression symptoms. Plasma TNF-α levels correlated with PCS and PTSD symptoms. The total number of mTBIs correlated with exosomal and plasma NfL levels and plasma IL-6. Increased number of years since the most recent TBI correlated with higher exosomal NfL and lower plasma IL-6 levels, while increased number of years since first TBI correlated with higher levels of exosomal and plasma NfL, as well as plasma TNF-α and VEGF.
Conclusion Repetitive mTBIs are associated with elevated exosomal and plasma levels of NfL, even years following these injuries, with the greatest elevations in those with chronic PCS, PTSD, and depression symptoms. Our results suggest a possible neuroinflammatory and axonal disruptive basis for symptoms that persist years after mTBI, especially repetitive.
Glossary
- AOC=
- alteration of consciousness;
- CENC=
- Chronic Effects of Neurotrauma Consortium;
- DoD=
- Department of Defense;
- DRRI-2=
- Deployment Risk and Resiliency Inventory–2;
- DSM-IV=
- Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
- DSM-5=
- Diagnostic and Statistical Manual of Mental Disorders, 5th edition;
- GLM=
- generalized linear model;
- IL=
- interleukin;
- IQR=
- interquartile range;
- IRB=
- institutional review board;
- LOC=
- loss of consciousness;
- mTBI=
- mild traumatic brain injury;
- NfL=
- neurofilament light;
- NSI=
- Neurobehavioral Symptom Inventory;
- OEF=
- Operation Enduring Freedom;
- OIF=
- Operation Iraqi Freedom;
- OND=
- Operation New Dawn;
- PCE=
- possible concussive event;
- PCL-M=
- PTSD Checklist Military Version;
- PCS=
- postconcussive syndrome;
- PHQ-9=
- 9-item Patient Health Questionnaire Depression Scale;
- PTA=
- posttraumatic amnesia;
- PTSD=
- posttraumatic stress disorder;
- SM=
- service members;
- TBI=
- traumatic brain injury;
- TNF=
- tumor necrosis factor;
- VA=
- Veterans Affairs;
- VCU rCDI=
- Virginia Commonwealth University Retrospective Concussion Diagnostic Interview;
- VEGF=
- vascular endothelial growth factor
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
CENC Multisite Observational Study coinvestigators are listed in the appendix 2 at the end of the article.
See page 1017
Podcast: NPub.org/7mc8bk
- Received July 22, 2019.
- Accepted in final form December 2, 2019.
- © 2020 American Academy of Neurology
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- Author response: Exosomal neurofilament light: A prognostic biomarker for remote symptoms after mild traumatic brain injury?
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