Uncovering the Role of Thrombospodin-1 and Occludin as Potential Prognostic and Diagnostic Biomarkers in Traumatic Brain Injury

TL;DR

This study explores thrombospondin-1 and occludin as potential biomarkers for diagnosing and predicting outcomes in traumatic brain injury patients.

Contribution

The study identifies TSP-1 and occludin as novel biomarkers for TBI prognosis and diagnosis.

Findings

Lower serum TSP-1 levels correlate with poor patient outcomes at 6 months.

Occludin shows potential as a biomarker for prognosis and mild TBI diagnosis, though with limited discriminative power.

TSP-1-deficient animals exhibit worsened TBI conditions, highlighting TSP-1's role in BBB integrity and inflammation.

Abstract

Traumatic brain injury (TBI) is a highly heterogeneous disease and achieving an accurate diagnosis remains a significant challenge. Biomarkers play a crucial role in minimizing the reliance on invasive techniques like computed tomography, which also have significant economic costs. Human samples were obtained from prospective cohort studies. Mice were subjected to an experimental model of traumatic brain injury. Biomarker levels, gene expression, and blood–brain barrier integrity were analyzed using ELISA, qRT-PCR, and Evans Blue assay; data were statistically evaluated using parametric or non-parametric tests as appropriate. This study focuses on evaluating the role of matricellular protein thrombospondin-1 (TSP-1) and the tight junction proteins occludin and ZO-1 as potential biomarkers of TBI. We showed that lower serum TSP-1 levels correlated with poor patient outcomes at 6 months compared to those patients with a good outcome. Additionally, the disruption of the blood–brain barrier (BBB) and subsequent release of tight junction proteins allowed us to identify occludin as a potential biomarker for prognosis in a cohort of TBI patients and as a diagnosis biomarker in a subgroup of patients with mild TBI, but its discriminative power as a diagnosis biomarker appears modest, as reflected by an AUC of 0.693. On the other hand, ZO-1 exhibited increased levels but limited diagnostic utility. These findings highlight the critical role of TSP-1 in maintaining BBB integrity and regulating the inflammatory response after a TBI, supported by the worsened condition observed in TSP-1-deficient animals. These results demonstrate the potential of TSP-1 and occludin as valuable biomarkers for secondary injury and disease progression in patients with mild to moderate/severe TBI.

Figures