Thus, some issues have to be considered by researchers as experimental CVST models present several technical challenges and display different features depending on each technical approach (Table 1, Figure 1). In rodents, almost all models require invasive approaches with prior exposure of sinuses and veins by craniotomy, which may induce iatrogenic parenchymal damages. 4, 18 An endovascular approach is rarely used, as it requires available intravascular imaging techniques to obtain a reproducible location of thrombus and is rather performed in large animal models. Particularly, the superior sagittal sinus (SSS) is an interesting target, as it constitutes the main location of CVST in human. 17 Cerebral cortical veins and dural venous sinuses are commonly targeted to trigger thrombosis. In experimental models, CVST is induced either by vascular wall injury, blood flow restriction, or coagulation activation, defined as cornerstones of thrombosis in the Virchow's triad. Herein, we review different common rodent models, their strengths and limitations, as well as, their contribution over the last decades to the knowledge of CVST. 15, 16 Still, the use of rodents allows use of genetically modified strains, which offer the opportunity to elucidate the potential role of genes involved in CVST. 14 Considering differences between the cerebral venous network in rodents and humans and numerous anastomosis, it remains difficult to obtain models relevant clinically.

In contrast to arterial ischemic stroke, only few experimental CVST models have been developed, mostly including small animals, such as rodents, rather than large animal models. Thus, a major preclinical approach for deciphering the patho-physiology of CVST and testing new therapeutics is the goal of animal models. Although guidelines do not currently support DOACs treatments during CVST, different reports suggested their sufficient safety and efficacy compared to VKAs, which require validation in larger studies. 11 Recently, direct oral anticoagulants (DOACs i.e., dabigatran, rivaroxaban, apixaban) were introduced providing new perspectives for CVST treatment. To date, no study has demonstrated any additional benefit of EVT over heparin in the setting of the acute phase. 1, 2, 10 EVT aims to achieve rapid recanalization compared to anticoagulants, which mainly prevent extension, embolization of the existing thrombus, and thrombosis recurrence. 4 Endovascular therapy (EVT) through local injection of fibrinolytic drugs (e.g., altepase, urokinase), mechanical thrombectomy, or both have been proposed to improve clinical outcome. 1, 2 Despite intensive anticoagulation treatment, ≈20% of patients with CVST will experience clinical deterioration or maintain their disability.

1, 2, 6 This may be the result, at least in part, of the improved availability and performance of brain imaging, leading to better diagnosis and identification of less severe cases over the past decades.īased upon the limited evidence available compared to common VTE, 9 initial anticoagulation with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH) bridging with vitamin K antagonists (VKAs) is currently recommended, regardless of the presence of ICH. 3–5 million per year, respectively) with an overall death and dependency rate ≈15%. 4, 5, 7, 8 Recent studies reported higher incidence of CVST than previously estimated (13–17.5 vs. Clinical symptoms range from isolated headaches (the most frequent one at presentation ≈90%), to focal deficits, seizure, and coma. Clinical symptoms result from increased intracranial pressure due to impaired venous drainage and CVST-related brain injury. 4- 7 Diagnosis and prognosis are still challenging due to the non-specificity and high variability of clinical course.

3 Beyond thrombosis, CVST-related parenchymal injuries include edema, ischemic strokes, and intra-cerebral hemorrhage (ICH i.e., parenchymal/subdural hematomas and subarachnoid hemorrhages), which are identified in 40%–60% of patients. 1, 2 Predisposing factors for CVST are multiple, including those described in VTE and specific local causes (regional infections, brain tumors, and cranial trauma). Cerebral venous sinus thrombosis (CVST) is an uncommon location of venous thromboembolism (VTE) that represents a distinct cause of stroke primarily affecting young adults.

Cerebrum dispersio midi