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

Xuan Vinh To; Patrick Donnelly; Liam Maclachlan; Kate Mahady; Eduardo Miguel Apellaniz; Paul Cumming; Craig Winter; Fatima Nasrallah

doi:10.1016/j.bbih.2023.100653

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

Brain Behav Immun Health. 2023 Jun 22:31:100653. doi: 10.1016/j.bbih.2023.100653. eCollection 2023 Aug.

Authors

Xuan Vinh To¹, Patrick Donnelly², Liam Maclachlan^{2

3}, Kate Mahady⁴, Eduardo Miguel Apellaniz², Paul Cumming^{5

6}, Craig Winter^{2

7

8}, Fatima Nasrallah²

Affiliations

¹ Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
² Department of Neurosurgery, Royal Brisbane and Women's Hospital, Brisbane, Australia.
³ School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, Australia.
⁴ Department of Radiology, Royal Brisbane and Women's Hospital, Brisbane, Australia.
⁵ Department of Nuclear Medicine, Bern University Hospital, Bern, Switzerland.
⁶ School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia.
⁷ Faculty of Medicine, University of Queensland, Brisbane, Australia.
⁸ School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Australia.

Abstract

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.

Keywords: Blood-brain barrier dysfunction; Cerebral contusion; Cerebral microbleed; Dynamic contrast enhancement; Micro haemorrhage; Susceptibility-weighted imaging; Traumatic brain injury.