EXPRESS: A novel mouse model of cerebral venous sinus thrombosis based on photochemical-induction combined with in situ injection.

Abstract

Cerebral venous sinus thrombosis (CVST) is a distinct cerebrovascular disorder characterized by impaired venous drainage and blood-brain barrier dysfunction, yet its pathophysiology remains poorly understood due to a lack of refined experimental models. We developed a novel, clinically relevant mouse model of CVST by integrating localized intraluminal induction with photochemical occlusion of the superior sagittal sinus (SSS). Model fidelity was validated using laser speckle contrast imaging, MRI, and histological analysis. Our approach produced consistent, spatially restricted SSS thrombosis, resulting in pronounced acute-stage brain edema and venous infarction. Notably, MRI combined with TTC staining identified a peri-infarct region suggestive of a venous penumbra. Functional assessments revealed significant acute motor deficits followed by recovery at day 7, whereas cognitive impairments persisted longer. Compared with conventional FeCl₃ or systemic Rose Bengal photothrombosis models, this integrated method exhibited superior anatomical specificity and minimized off-target tissue injury. This study introduces a reproducible CVST model that successfully recapitulates the key hemodynamic and pathological features of human venous stroke, providing a robust platform for mechanistic investigations and the evaluation of targeted therapeutic interventions.