Endothelial glycocalyx shedding and oxidative stress in neuronal damage after return of spontaneous circulation in cardiac arrest.

Endothelial glycocalyx (eGC) covers the luminal surface of all vessels. Recent evidence has highlighted its pivotal role in maintaining the integrity of the blood-brain barrier (BBB). Return of spontaneous circulation (ROSC) after cardiac arrest (CA) is a main example of global ischemia-reperfusion (I/R) injury. I/R injury can induce eGC shedding and redox imbalance. This study aims to evaluate the interplay between eGC shedding and oxidative stress (OS) in determing neuronal injury and predicting neurological outcomes following CA. Blood and urine samples were obtained from patients who achieved ROSC after CA. Biomarkers of eGC shedding (syndecan-1 [SDC-1], CD44s, hyaluronan [HYAL], and sulfated glycosaminoglycans [GAGs], of endothelial injury (thrombomodulin [TBML]), of OS (malondialdehyde [MDA], total hydroperoxides [H₂O₂], total antioxidant capacity [CAT], reduced glutathione [GSH], superoxide dismutase [SOD]), and inflammatory mediators (IL-6 and TNF-α) were measured. Neuron-specific enolase (NSE) levels were employed as a surrogate marker of neuronal injury. A score ≥ 4 in the modified Rankin Scale (mRS) at 28 days was considered as poor neurological outcome. Seventy-one patients were included. The levels of SDC-1, HYAL, CD44s, TBML, TAC, SOD, H₂O₂, IL-6, and TNF-α were statistically correlated with neuronal injury. Higher levels of SDC-1, HYAL, CD44s, TBML, MDA, and SOD were observed in patients with poor neurological outcomes. Multivariable logistic regression identified SDC-1 > 796 ng/mL (p = 0.02), TBML > 446 pg/mL (p = 0.03), and MDA > 179 nmol/g (p = 0.03), as predictors of unfavorable neurological outcomes. eGC shedding and OS are interrelated key pathophysiological mechanisms contributing to neuronal injury following CA.