Systemic endothelial glycocalyx shedding mediates vascular hyperpermeability after traumatic brain injury.

Background: In traumatic brain injury (TBI), the primary insult initiates a secondary cascade that exacerbates neuronal injury. Blood-brain barrier (BBB) dysfunction plays a central role in this process, leading to vascular leakage and vasogenic edema. Recent evidence suggests that the endothelial glycocalyx (eGC) is an essential structural component of the BBB. This study aimed to determine whether systemic eGC shedding after TBI contributes to vascular hyperpermeability and cerebral edema. Methods: We enrolled patients within 24 h of TBI. Blood and urine samples were collected to measure biomarkers of eGC shedding [syndecan-1 (SDC-1), soluble CD44 (CD44s), hyaluronan (HA), sulfated glycosaminoglycans (GAGs)], of endothelial cell damage [thrombomodulin (sTM)], of inflammation [interleukin-6 (IL-6)], and of vascular permeability [microalbuminuria]. Neuron-specific enolase (NSE) was measured as a surrogate marker of neuronal injury and BBB disruption. eGC thickness was estimated via sublingual microcirculation capillaroscopy using the perfused boundary region (PBR)-an inverse parameter of eGC thickness. Cranial computed tomography (CT) was used to assess signs of cerebral edema. A modified Rankin Scale (mRS) score ≥4 at 3 months was considered a poor neurological outcome. Results: We enrolled 55 TBI patients, and 20 healthy individuals served as controls. Compared with controls, TBI patients had significantly higher SDC-1, CD44s, GAGs, sTM, IL-6, NSE, and microalbuminuria levels, as well as higher adjusted PBR values. The levels of SDC-1, CD44s, sTM, IL-6, and microalbuminuria showed a statistically significant correlation with NSE levels. Additionally, a significant positive correlation was observed between microalbuminuria levels and adjusted PBR. Microalbuminuria was higher in those with cistern compression on CT and in those with poor neurological outcomes. Conclusion: Systemic eGC shedding appears to be an early and central pathophysiological event after TBI, contributing to systemic vascular hyperpermeability and thereby to the development of cerebral edema.