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

Background: 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. Methods: 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. Results: This work 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 outcome 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. Conclusions: These findings highlight the critical role of TSP-1 in maintaining the BBB integrity and regulating the inflammatory response after 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.