Oxidative stress and increased formation of vasoconstricting F2-isoprostanes in patients with reversible cerebral vasoconstriction syndrome

Abstract

The pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS) is unknown. Oxidative stress is detrimental to endothelial function and vascular reactivity. We hypothesized that the oxidative stress marker 8-iso-prostaglandin F2α, which is also a potent vasoconstrictor, might contribute to the pathogenesis of RCVS. Recruited participants included 103RCVS patients, 53 patients with primary headache with acute severe attacks, and 54 healthy controls. Subjects recruited prior to 2009 were discovery cohort, whereas those after 2009, replication cohort. Urine samples were obtained from all patients at registration and from 79 patients with RCVS again at remission stage. Urine 8-iso-prostaglandin F2α was analyzed by liquid chromatography-tandem mass spectrometry. Patients with RCVS received magnetic resonance angiography and transcranial color-coded sonography. In RCVS patients, the urine 8-iso-prostaglandin F2α level was higher than that in the other groups in discovery, replication, and combined cohorts (RCVS, 0.29±0.18; primary headache with acute severe attacks, 0.21±0.19; control, 0.18±0.09ng/mg creatinine; P<0.001), and it was positively correlated with the flow velocities of major intracranial arteries, especially within the first week of disease onset (middle cerebral artery, Spearman's correlation coefficient [rs]=0.580, P=0.002; anterior cerebral artery, rs=0.472, P=0.042; posterior cerebral artery, rs=0.457, P=0.022; basilar artery, rs= 0.530, P=0.002). The 8-iso-prostaglandin F2α level decreased from the ictalto remission stage in RCVS patients (0.31±0.21 vs 0.16±0.10ng/mg creatinine, P<0.001). 8-Iso-prostaglandin F2α was higher in patients with RCVS and correlated with the severity of vasoconstrictions. Further studies are required to explore its potential pathogenic role.

Keywords: 8-Iso-prostaglandin F(2α); Endothelial dysfunction; Oxidative stress; Reversible cerebral vasoconstriction syndrome; Thunderclap headaches.