Cervical artery tortuosity is associated with intracranial aneurysm.

Background Intracranial aneurysms may be associated with an underlying arteriopathy, leading to arterial wall fragility. Arterial tortuosity is a major characteristic of some connective tissue disease. Aim To determine whether intracranial aneurysm is associated with an underlying arteriopathy. Methods Using a case-control design, from May 2012 to May 2013, we selected intracranial aneurysm cases and controls from consecutive patients who had conventional cerebral angiography in our center. Cases were patients with newly diagnosed intracranial aneurysm. Controls were patients who had diagnostic cerebral angiography and free of aneurysm. The prevalence of tortuosity, retrospectively assessed according to standard definitions, was compared between cases and controls and, association between tortuosity and some aneurysm characteristics was examined, in cases only. Results About 659 arteries from 233 patients (112 cases and 121 controls) were examined. Tortuosity was found in 57 (51%) cases and 31 (26%) controls (adjusted OR = 2.71; 95%CI, 1.53-4.80). The same trend was found when looking at each tortuosity subtype (simple tortuosity, coil, kink) or at carotid or vertebral territory separately. In contrast, no association between tortuosity and rupture status, aneurysm number or neck size was found. Conclusions Cervical artery tortuosity is significantly associated with intracranial aneurysm, although not related to main aneurysm characteristics. Our results support the presence of an underlying diffuse arteriopathy in intracranial aneurysm patients.

Hyperfibrinolysis increases blood-brain barrier permeability by a plasmin- and bradykinin-dependent mechanism.

Hyperfibrinolysis is a systemic condition occurring in various clinical disorders such as trauma, liver cirrhosis, and leukemia. Apart from increased bleeding tendency, the pathophysiological consequences of hyperfibrinolysis remain largely unknown. Our aim was to develop an experimental model of hyperfibrinolysis and to study its effects on the homeostasis of the blood-brain barrier (BBB). We induced a sustained hyperfibrinolytic state in mice by hydrodynamic transfection of a plasmid encoding for tissue-type plasminogen activator (tPA). As revealed by near-infrared fluorescence imaging, hyperfibrinolytic mice presented a significant increase in BBB permeability. Using a set of deletion variants of tPA and pharmacological approaches, we demonstrated that this effect was independent of N-methyl-D-aspartate receptor, low-density lipoprotein-related protein, protease-activated receptor-1, or matrix metalloproteinases. In contrast, we provide evidence that hyperfibrinolysis-induced BBB leakage is dependent on plasmin-mediated generation of bradykinin and subsequent activation of bradykinin B2 receptors. Accordingly, this effect was prevented by icatibant, a clinically available B2 receptor antagonist. In agreement with these preclinical data, bradykinin generation was also observed in humans in a context of acute pharmacological hyperfibrinolysis. Altogether, these results suggest that B2 receptor blockade may be a promising strategy to prevent the deleterious effects of hyperfibrinolysis on the homeostasis of the BBB.