Release of Hyaluronan in Aneurysmal Subarachnoid Hemorrhage and Cerebral Vasospasm: A Pilot Study Indicating a Shedding of the Endothelial Glycocalyx.

ABSTRACT

BACKGROUND: This pilot study investigated plasma concentrations of hyaluronan, heparan sulfate, and syndecan-1 as possible biomarkers for glycocalyx integrity after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Daily blood samples for biomarker assay were obtained in aSAH patients on the intensive care unit stay and compared with samples from a historic cohort of 40 healthy controls. In post hoc subgroup analyses in patients with and without cerebral vasospasm, we explored the influence of aSAH-related cerebral vasospasm on biomarker levels. RESULTS: A total of 18 aSAH patients and 40 historic controls were included in the study. Median (interquartile range) plasma levels of hyaluronan were higher in aSAH patients compared with controls (131 [84 to 179] vs. 92 [82 to 98] ng/mL, respectively; P=0.009), whereas heparan sulfate (mean±SD 754±428 vs. 1329±316 ng/mL; P<0.001) and syndecan-1 (median 23 [17 to 36] vs. 30 [23 to 52] ng/mL; P=0.02) levels were lower. Patients who developed vasospasm had significantly higher median hyaluronan concentrations at day 7 (206 [165 to 288] vs. 133 [108 to 164] ng/mL, respectively; P=0.009) and at day of first vasospasm detection (203 [155 to 231] vs. 133 [108 to 164] ng/mL, respectively; P=0.01) compared with those without vasospasm. Heparan sulfate and syndecan-1 concentrations were similar in patients with and without vasospasm. CONCLUSIONS: The increased plasma concentrations of hyaluronan after aSAH suggest selective shedding of this component of the glycocalyx. Increased levels of hyaluronan in patients with cerebral vasospasm, underlines a potential role for hyaluronan in vasospasm processes.