Anti-inflammatory interleukin 1 receptor antagonist concentration in plasma correlates with blood-brain barrier integrity in the primary lesion area in traumatic brain injury patients.
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BORIS DOI
Publisher DOI
PubMed ID
37415924
Description
PURPOSE
Blood-brain barrier (BBB) dysregulation and pro-inflammatory signalling molecules are secondary factors that have been associated with injury severity and long-term clinical outcome following traumatic brain injury (TBI). However, the association between BBB permeability and inflammation is unknown in human TBI patients. In this study, we investigated whether BBI integrity as measured by Dynamic Contrast-Enhanced (DCE) Magnetic Resonance Imaging (MRI) correlates with plasma levels of immunological markers following TBI.
METHODS
Thirty-two TBI patients recruited from a neurosurgical unit were included in the study. Structural three-dimensional T1-weighted and DCE-MRI images were acquired on a 3T MRI at the earliest opportunity once the participant was sufficiently stable after patient admission to hospital. Blood sampling was performed on the same day as the MRI. The location and extents of the haemorrhagic and contusional lesions were identified. Immunological biomarkers were quantified from the participants' plasma using a multiplex immunoassay. Demographic and clinical information, including age and Glasgow Coma Scale (GCS) were also collected and the immunological biomarker profiles were compared across controls and the TBI severity sub-groups. Contrast agent leakiness through blood-brain barriers (BBB) in the contusional lesions were assessed by fitting DCE-MRI using Patlak model and BBB leakiness characteristics of the participants were correlated with the immunological biomarker profiles.
RESULTS
TBI patients showed reduced plasma levels of interleukin (IL)-1β, IFN-γ, IL-13, and chemokine (C-C motif) ligands (CCL)2 compared to controls and significantly higher levels of platelet-derived growth factor (PDGF-BB), IL-6, and IL-8. BBB leakiness of the contusional lesions did not significantly differ across different TBI severity sub-groups. IL-1ra levels significantly and positively correlated with the contusional lesion's BBB integrity as measured with DCE-MRI via an exponential curve relationship.
DISCUSSION
This is the first study to combine DCE-MRI with plasma markers of inflammation in acute TBI patients. Our finding that plasma levels of the anti-inflammatory cytokine IL-1ra correlated negatively with increased leakiness of the BBB.
Blood-brain barrier (BBB) dysregulation and pro-inflammatory signalling molecules are secondary factors that have been associated with injury severity and long-term clinical outcome following traumatic brain injury (TBI). However, the association between BBB permeability and inflammation is unknown in human TBI patients. In this study, we investigated whether BBI integrity as measured by Dynamic Contrast-Enhanced (DCE) Magnetic Resonance Imaging (MRI) correlates with plasma levels of immunological markers following TBI.
METHODS
Thirty-two TBI patients recruited from a neurosurgical unit were included in the study. Structural three-dimensional T1-weighted and DCE-MRI images were acquired on a 3T MRI at the earliest opportunity once the participant was sufficiently stable after patient admission to hospital. Blood sampling was performed on the same day as the MRI. The location and extents of the haemorrhagic and contusional lesions were identified. Immunological biomarkers were quantified from the participants' plasma using a multiplex immunoassay. Demographic and clinical information, including age and Glasgow Coma Scale (GCS) were also collected and the immunological biomarker profiles were compared across controls and the TBI severity sub-groups. Contrast agent leakiness through blood-brain barriers (BBB) in the contusional lesions were assessed by fitting DCE-MRI using Patlak model and BBB leakiness characteristics of the participants were correlated with the immunological biomarker profiles.
RESULTS
TBI patients showed reduced plasma levels of interleukin (IL)-1β, IFN-γ, IL-13, and chemokine (C-C motif) ligands (CCL)2 compared to controls and significantly higher levels of platelet-derived growth factor (PDGF-BB), IL-6, and IL-8. BBB leakiness of the contusional lesions did not significantly differ across different TBI severity sub-groups. IL-1ra levels significantly and positively correlated with the contusional lesion's BBB integrity as measured with DCE-MRI via an exponential curve relationship.
DISCUSSION
This is the first study to combine DCE-MRI with plasma markers of inflammation in acute TBI patients. Our finding that plasma levels of the anti-inflammatory cytokine IL-1ra correlated negatively with increased leakiness of the BBB.
Date of Publication
2023-08
Publication Type
Article
Subject(s)
Keyword(s)
Blood-brain barrier dysfunction Cerebral contusion Cerebral microbleed Dynamic contrast enhancement Micro haemorrhage Susceptibility-weighted imaging Traumatic brain injury
Language(s)
en
Contributor(s)
To, Xuan Vinh | |
Donnelly, Patrick | |
Maclachlan, Liam | |
Mahady, Kate | |
Apellaniz, Eduardo Miguel | |
Winter, Craig | |
Nasrallah, Fatima |
Additional Credits
Series
Brain, behavior, & immunity - health
Publisher
Elsevier
ISSN
2666-3546
Access(Rights)
open.access