Concomitant Traumatic Brain Injury Exacerbates Endotheliopathy in Patients with Spinal Cord Injury

Neurotrauma can cause endothelial dysfunction, characterized by neurovascular barrier disruption, tissue edema, neuroinflammation, and coagulation abnormalities, all of which may contribute to secondary injuries and worsened clinical outcomes. Here, we assess the effect of different types of neurotrauma on the local levels of biomarkers of endothelial injury and inflammation. Cerebrospinal fluid (CSF) samples were collected at multiple time points from patients with isolated traumatic spinal cord injury (SCI) and patients with concomitant SCI and traumatic brain injury (TBI). CSF levels of analytes associated with endothelial damage, as well as inflammatory mediators, were measured. Compared with patients with isolated SCI, those with SCI + TBI demonstrated significantly elevated CSF levels of multiple biomarkers linked to endotheliopathy and inflammation. In the presence of TBI, the highest increases in CSF levels of endothelial markers were observed for matrix metalloproteinase 10 (MMP-10), vascular endothelial growth factor A (VEGF-A), and fibroblast growth factor 2 (FGF-2). Among inflammatory factors, thymic stromal lymphopoietin (TSLP) showed the most pronounced difference in CSF content in patients with SCI + TBI compared with those with SCI alone, followed by interferon α2 (IFNα2) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Interestingly, CSF levels of MMP-1, MMP-10, VEGF-A, IFNα2, and TSLP significantly correlated with injury severity score. Our findings indicate that, in the presence of concomitant TBI, patients with SCI exhibit higher CSF levels of biomarkers associated with endotheliopathy, blood-brain barrier breakdown, protease-mediated degradation of endothelial glycocalyx, and neuroinflammation. These results identify potential theranostic biomarkers to stratify high-risk patients and mitigate neurovascular damage, thereby improving clinical outcomes.