Flow diverters have drastically changed the landscape of intracranial aneurysm treatment and are now considered first-line therapy for select lesions. Their mechanism of action relies on intrinsic alteration in hemodynamic parameters, both at the parent artery and within the aneurysm sac. Moreover, the device struts act as a nidus for endothelial cell growth across the aneurysm neck ultimately leading to aneurysm exclusion from the circulation. In silico computational analyses and investigations in preclinical animal models have provided valuable insights into the underlying biological basis for flow diverter therapy. Here, we review the present understanding pertaining to flow diverter biology and mechanisms of action, focusing on stent design, induction of intra-aneurysmal thrombosis, endothelialization, and alterations in hemodynamics.
BackgroundCharacterization of acute ischemic stroke (AIS) clots has typically focused on two-dimensional histological analysis of the thrombus. The three-dimensional (3D) architecture and distribution of components within emboli have not been fully investigated. The aim of this study was to examine the composition and microstructure of AIS clots using histology and serial block-face scanning electron microscopy (SBFSEM).MethodsAs part of the multi-institutional STRIP registry, 10 consecutive AIS emboli were collected from 10 patients treated by mechanical thrombectomy. Histological and immunohistochemical analysis was performed to determine clot composition. SBFSEM was used to assess the ultrastructural organization of the clots and specific features of individual components.ResultsQuantification of Martius Scarlett Blue stain identified fibrin (44.4%) and red blood cells (RBCs, 32.6%) as the main components. Immunohistochemistry showed a mean platelet and von Willebrand factor content of 23.9% and 11.8%, respectively. The 3D organization of emboli varied greatly depending on the region analyzed. RBC-rich areas were composed mainly of tightly packed RBCs deformed into polyhedrocytes with scant fibrin fibers interwoven between cells. The regions with mixed composition showed thick fibrin fibers along with platelets, white blood cells and RBC clusters. Fibrin-rich areas contained dense fibrin masses with sparse RBC. In three cases, the fibrin formed a grid-like or a sponge-like pattern, likely due to thrombolytic treatment. Segmentation showed that fibrin fibers were thinner and less densely packed in these cases.Conclusions3D-SEM provides novel and potentially clinically relevant information on clot components and ultrastructure which may help to inform thrombolytic treatment and medical device design.
BACKGROUND AND PURPOSE:The safety of placing multiple overlapped endoluminal flow diverters remains unclear because small eloquent branch arteries theoretically could become occluded by these devices. We placed single and multiple flow diverters over small branch arteries in rabbit aortas to determine the incidence of branch artery occlusion.
Elastase injection through the cisterna magna can induce intracranial dolichoectasia in mice. Fifteen to 25 mu of elastase is an appropriate dose to use with acceptable mortality.
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