DEVELOPING A MURINE MODEL OF CEREBRAL VENOUS THROMBOSIS FOR PRECLINICAL RESEARCH

Cerebral venous thrombosis (CVT) is a less common form of stroke with a higher incidence in younger adults. Causes of cerebral sinus and/or vein occlusion and the accompanying brain parenchymal damage remain unexplained. Progress is hindered by clinical heterogeneity, low incidence, and preclinical models that mostly rely on permanent superior sagittal sinus occlusion. These models do not reflect the human disease, in which spontaneous or treatment-driven recanalization is common, nor do they clarify how recanalization influences parenchymal damage. Since current therapies primarily focus on restoring venous patency, our aim is to develop a CVT model that replicates thrombosis with subsequent recanalization to study downstream brain injury and potential neuroprotective strategies.
We established a mouse CVT model using retro-orbital administration of INU1-Fab antibody with weight-adjusted dose titration. Neurological deficits scores were recorded on days 1, 5, and 7. Brains were harvested after D7 for histopathological confirmation of venous thrombosis and characterization of parenchymal changes.
INU1-Fab produced a mild, transient phenotype: mice showed reduced exploratory activity during the first ~120 min post-injection, then returned to baseline. On D1, Rotarod and OpenField tests were significantly impaired in model group vs sham/controls. By D7, histopathology demonstrated bilateral focal-to-multifocal lesions in deep gray structures, with vacuolation, neutrophil rarefaction, and reactive gliosis in H&E and Iba-1 staining, features consistent with cytotoxic edema.
Preliminary data indicate that INU1-Fab reliably induces a CVT phenotype accompanied by secondary parenchymal changes. These findings evidence the use of this preclinical model to study potential therapies with ultimately successful translation to patients.