Diffusion tensor imaging and plasma immunological biomarker panel in a rat traumatic brain injury (TBI) model and in human clinical TBI

Abstract

Introduction: Neuroinflammatory reactions play a significant role in the pathology and long-term consequences of traumatic brain injury (TBI) and may mediate salutogenic processes that white matter integrity. This study aimed to investigate the relationship between inflammatory markers and white matter integrity following TBI in both a rat TBI model and clinical TBI cases. Methods: In the rat model, blood samples were collected following a controlled cortical impact (CCI) to assess a panel of inflammatory markers; MR-based diffusion tensor imaging (DTI) was employed to evaluate white matter integrity 60 days post-injury. 15 clinical TBI patients were similarly assessed for a panel of inflammatory markers and DTI post-intensive care unit discharge. Blood samples from healthy controls were used for comparison of the inflammatory markers. Results: Time-dependent elevations in immunological markers were observed in TBI rats, with a correlation to preserved fractional anisotropy (FA) in white matter. Specifically, TBI-induced increased plasma levels of IL-1β, IL-6, G-CSF, CCL3, CCL5, and TNF-α were associated with higher white matter integrity, as measured by FA. Clinical cases had similar findings: elevated inflammatory markers (relative to controls) were associated with preservation of FA in vulnerable white matter regions. Discussion: Inflammatory markers in post-TBI plasma samples are ambivalent with respect to prediction of favourable outcome versus a progression to more pervasive pathology and morbidity.