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...

Full description

Bibliographic Details
Main Authors: Katie A. Edwards, Cassandra L. Pattinson, Vivian A. Guedes, Jordan Peyer, Candace Moore, Tara Davis, Christina Devoto, L. Christine Turtzo, Lawrence Latour, Jessica M. Gill
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