Experimental Models of Cerebral Venous Sinus Thrombosis: Induction Techniques, Species Considerations, and Translational Insights

Summary

This review systematically compares experimental CVST animal models, evaluating induction methods, species, reversibility, severity, feasibility, reproducibility, limitations, and translational value to guide rational selection among existing models.

Abstract

Cerebral venous sinus thrombosis (CVST) is a rare but life-threatening cerebrovascular disorder for which animal models are essential for mechanistic and translational research. This review systematically synthesizes experimental CVST models across species and induction techniques using predefined criteria, including thrombus composition, reversibility, severity, reproducibility, technical feasibility, and clinical relevance. The successful establishment of CVST models is defined by direct evidence of sinus occlusion, with parenchymal lesions considered optional. Thrombosis induced by FeCl₃ or photochemical methods is generally reversible, whereas models based on permanent ligation, autologous clot injection, balloon catheter combined with thrombin, or water-swellable rubber result in irreversible occlusion.

Most models induce mild pathology, while severe phenotypes usually require combined interventions such as balloon catheter inflation with thrombin, complete ligation with thrombin, or partial ligation with thrombin injection and FeCl₃ application. Ligation-only models exhibit low reproducibility, whereas photochemical and balloon catheter-based models are limited by specialized equipment and technical expertise requirements. In terms of translational relevance, large-animal balloon catheter models combined with thrombogenic agents and rodent clot-injection models are most clinically applicable. Thrombolysis or recanalization studies should preferentially employ reversible models while avoiding permanent ligation or rigid occlusive devices. Water-swellable rubber-based models are particularly suitable for studying slowly progressive forms of CVST. Intravascular device validation studies should prioritize swine models using balloon catheters in combination with thrombogenic agents. In addition, developing etiology-specific models may facilitate the preclinical evaluation of targeted, mechanism-based therapeutic approaches, while non-human primate models may further enhance translational relevance.

Introduction

Cerebral venous sinus thrombosis (CVST) is a rare but potentially life-threatening cerebrovascular disorder characterized by thrombosis in dural venous sinuses or cerebral veins¹. Unlike arterial stroke, CVST predominantly affects young adults, especially women of childbearing age, and exhibits diverse clinical presentations, ranging from headache and papilledema to seizures, focal neurological deficits, and venous infarction^2,3. The underlying pathophysiology is multifactorial, involving venous stasis, endothelial injury, and hypercoagulability. Additional contributing factors include ....