Inflammatory Cytokines Associate With Neuroimaging After Acute Mild Traumatic Brain Injury
Introduction: Elevated levels of blood-based proinflammatory cytokines are linked to acute moderate to severe traumatic brain injuries (TBIs), yet less is known in acute mild (m)TBI cohorts. The current study examined whether blood-based cytokines can differentiate patients with mTBI, with and witho...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2020-05-01
|
Series: | Frontiers in Neurology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2020.00348/full |
_version_ | 1818259629328564224 |
---|---|
author | Katie A. Edwards Katie A. Edwards Cassandra L. Pattinson Vivian A. Guedes Jordan Peyer Candace Moore Tara Davis Tara Davis Christina Devoto Christina Devoto L. Christine Turtzo Lawrence Latour Jessica M. Gill Jessica M. Gill |
author_facet | Katie A. Edwards Katie A. Edwards Cassandra L. Pattinson Vivian A. Guedes Jordan Peyer Candace Moore Tara Davis Tara Davis Christina Devoto Christina Devoto L. Christine Turtzo Lawrence Latour Jessica M. Gill Jessica M. Gill |
author_sort | Katie A. Edwards |
collection | DOAJ |
description | Introduction: Elevated levels of blood-based proinflammatory cytokines are linked to acute moderate to severe traumatic brain injuries (TBIs), yet less is known in acute mild (m)TBI cohorts. The current study examined whether blood-based cytokines can differentiate patients with mTBI, with and without neuroimaging findings (CT and MRI).Material and Methods: Within 24 h of a mTBI, determined by a Glasgow Coma Scale (GCS) between 13 and 15, participants (n = 250) underwent a computed tomography (CT) and magnetic resonance imaging (MRI) scan and provided a blood sample. Participants were classified into three groups according to imaging findings; (1) CT+, (2) MRI+ (CT–), (3) Controls (CT– MRI–). Plasma levels of circulating cytokines (IL-6, IL-10, TNFα), and vascular endothelial growth factor (VEGF) were measured using an ultra-sensitive immunoassay.Results: Concentrations of inflammatory cytokines (IL-6, TNFα) and VEGF were elevated in CT+, as well as MRI+ groups (p < 0.001), compared to controls, even after controlling for age, sex and cardiovascular disease (CVD)-related risk factors; hypertension, and hyperlipidemia. Post-concussive symptoms were associated with imaging groupings, but not inflammatory cytokines in this cohort. Levels of VEGF, IL-6, and TNFα differentiated patients with CT+ findings from controls, with the combined biomarker model (VEGF, IL-6, TNFα, and IL-10) showing good discriminatory power (AUC 0.92, 95% CI 0.87–0.97). IL-6 was a fair predictor of MRI+ findings compared to controls (AUC 0.70, 95% CI 0.60–0.78). Finally, the combined biomarker model discriminated patients with MRI+ from CT+ with an AUC of 0.71 (95% CI 0.62–0.80).Conclusions: When combined, IL-6, TNFα, and VEGF may provide a promising biomarker cytokine panel to differentiate mTBI patients with CT+ imaging vs. controls. Singularly, IL-6 was a fair discriminator between each of the imaging groups. Future research directions may help elucidate mechanisms related to injury severity and potentially, recovery following an mTBI. |
first_indexed | 2024-12-12T18:18:29Z |
format | Article |
id | doaj.art-66c7dd25a4de44789bdfa8b61f9fb41a |
institution | Directory Open Access Journal |
issn | 1664-2295 |
language | English |
last_indexed | 2024-12-12T18:18:29Z |
publishDate | 2020-05-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Neurology |
spelling | doaj.art-66c7dd25a4de44789bdfa8b61f9fb41a2022-12-22T00:16:13ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-05-011110.3389/fneur.2020.00348534793Inflammatory Cytokines Associate With Neuroimaging After Acute Mild Traumatic Brain InjuryKatie A. Edwards0Katie A. Edwards1Cassandra L. Pattinson2Vivian A. Guedes3Jordan Peyer4Candace Moore5Tara Davis6Tara Davis7Christina Devoto8Christina Devoto9L. Christine Turtzo10Lawrence Latour11Jessica M. Gill12Jessica M. Gill13National Institutes of Health, National Institute of Nursing Research, Bethesda, MD, United StatesThe Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United StatesNational Institutes of Health, National Institute of Nursing Research, Bethesda, MD, United StatesNational Institutes of Health, National Institute of Nursing Research, Bethesda, MD, United StatesNational Institutes of Health, National Institute of Nursing Research, Bethesda, MD, United StatesNational Institutes of Health, National Institute of Nursing Research, Bethesda, MD, United StatesCenter for Neuroscience and Regenerative Medicine, Bethesda, MD, United StatesJohns Hopkins Suburban Hospital, Bethesda, MD, United StatesNational Institutes of Health, National Institute of Nursing Research, Bethesda, MD, United StatesThe Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United StatesNational Institutes of Health, National Institute of Neurological Disorders and Stroke, Bethesda, MD, United StatesNational Institutes of Health, National Institute of Neurological Disorders and Stroke, Bethesda, MD, United StatesNational Institutes of Health, National Institute of Nursing Research, Bethesda, MD, United StatesCenter for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Biomarker Core, Bethesda, MD, United StatesIntroduction: Elevated levels of blood-based proinflammatory cytokines are linked to acute moderate to severe traumatic brain injuries (TBIs), yet less is known in acute mild (m)TBI cohorts. The current study examined whether blood-based cytokines can differentiate patients with mTBI, with and without neuroimaging findings (CT and MRI).Material and Methods: Within 24 h of a mTBI, determined by a Glasgow Coma Scale (GCS) between 13 and 15, participants (n = 250) underwent a computed tomography (CT) and magnetic resonance imaging (MRI) scan and provided a blood sample. Participants were classified into three groups according to imaging findings; (1) CT+, (2) MRI+ (CT–), (3) Controls (CT– MRI–). Plasma levels of circulating cytokines (IL-6, IL-10, TNFα), and vascular endothelial growth factor (VEGF) were measured using an ultra-sensitive immunoassay.Results: Concentrations of inflammatory cytokines (IL-6, TNFα) and VEGF were elevated in CT+, as well as MRI+ groups (p < 0.001), compared to controls, even after controlling for age, sex and cardiovascular disease (CVD)-related risk factors; hypertension, and hyperlipidemia. Post-concussive symptoms were associated with imaging groupings, but not inflammatory cytokines in this cohort. Levels of VEGF, IL-6, and TNFα differentiated patients with CT+ findings from controls, with the combined biomarker model (VEGF, IL-6, TNFα, and IL-10) showing good discriminatory power (AUC 0.92, 95% CI 0.87–0.97). IL-6 was a fair predictor of MRI+ findings compared to controls (AUC 0.70, 95% CI 0.60–0.78). Finally, the combined biomarker model discriminated patients with MRI+ from CT+ with an AUC of 0.71 (95% CI 0.62–0.80).Conclusions: When combined, IL-6, TNFα, and VEGF may provide a promising biomarker cytokine panel to differentiate mTBI patients with CT+ imaging vs. controls. Singularly, IL-6 was a fair discriminator between each of the imaging groups. Future research directions may help elucidate mechanisms related to injury severity and potentially, recovery following an mTBI.https://www.frontiersin.org/article/10.3389/fneur.2020.00348/fullcytokinesneuroimagingmild traumatic brain injuryinflammationcardiovascular disease risk |
spellingShingle | Katie A. Edwards Katie A. Edwards Cassandra L. Pattinson Vivian A. Guedes Jordan Peyer Candace Moore Tara Davis Tara Davis Christina Devoto Christina Devoto L. Christine Turtzo Lawrence Latour Jessica M. Gill Jessica M. Gill Inflammatory Cytokines Associate With Neuroimaging After Acute Mild Traumatic Brain Injury Frontiers in Neurology cytokines neuroimaging mild traumatic brain injury inflammation cardiovascular disease risk |
title | Inflammatory Cytokines Associate With Neuroimaging After Acute Mild Traumatic Brain Injury |
title_full | Inflammatory Cytokines Associate With Neuroimaging After Acute Mild Traumatic Brain Injury |
title_fullStr | Inflammatory Cytokines Associate With Neuroimaging After Acute Mild Traumatic Brain Injury |
title_full_unstemmed | Inflammatory Cytokines Associate With Neuroimaging After Acute Mild Traumatic Brain Injury |
title_short | Inflammatory Cytokines Associate With Neuroimaging After Acute Mild Traumatic Brain Injury |
title_sort | inflammatory cytokines associate with neuroimaging after acute mild traumatic brain injury |
topic | cytokines neuroimaging mild traumatic brain injury inflammation cardiovascular disease risk |
url | https://www.frontiersin.org/article/10.3389/fneur.2020.00348/full |
work_keys_str_mv | AT katieaedwards inflammatorycytokinesassociatewithneuroimagingafteracutemildtraumaticbraininjury AT katieaedwards inflammatorycytokinesassociatewithneuroimagingafteracutemildtraumaticbraininjury AT cassandralpattinson inflammatorycytokinesassociatewithneuroimagingafteracutemildtraumaticbraininjury AT vivianaguedes inflammatorycytokinesassociatewithneuroimagingafteracutemildtraumaticbraininjury AT jordanpeyer inflammatorycytokinesassociatewithneuroimagingafteracutemildtraumaticbraininjury AT candacemoore inflammatorycytokinesassociatewithneuroimagingafteracutemildtraumaticbraininjury AT taradavis inflammatorycytokinesassociatewithneuroimagingafteracutemildtraumaticbraininjury AT taradavis inflammatorycytokinesassociatewithneuroimagingafteracutemildtraumaticbraininjury AT christinadevoto inflammatorycytokinesassociatewithneuroimagingafteracutemildtraumaticbraininjury AT christinadevoto inflammatorycytokinesassociatewithneuroimagingafteracutemildtraumaticbraininjury AT lchristineturtzo inflammatorycytokinesassociatewithneuroimagingafteracutemildtraumaticbraininjury AT lawrencelatour inflammatorycytokinesassociatewithneuroimagingafteracutemildtraumaticbraininjury AT jessicamgill inflammatorycytokinesassociatewithneuroimagingafteracutemildtraumaticbraininjury AT jessicamgill inflammatorycytokinesassociatewithneuroimagingafteracutemildtraumaticbraininjury |