Objective: The causes of cerebral sinus and vein occlusion and the accompanying parenchymal changes remain largely unexplained. The clinical variability and low incidence of the disease complicate systematic clinical investigations. Animal studies are indispensable; however, existing animal models of sinus thrombosis do not allow for long-term follow-up studies and are not suitable for pharmacological recanalization because sinus thrombosis is induced by ligation and injection of thrombogenic substances and does not resemble sinus thrombosis in humans.
Methods: We induced thrombosis of the superior sagittal sinus (SSS) by careful topical application of ferric chloride onto the SSS of rats, leading to highly reproducible occlusions. Magnetic resonance imaging was performed immediately after initiation of thrombosis and on postoperative Days 1, 2, and 7. Diffusion- and T2-weighted images allowed for calculation of the apparent diffusion coefficient and T2 relaxation time. Vascular status was assessed by venous magnetic resonance angiography. Neurological deficits were assessed with the rotarod test.
Results: Seven days after induction of thrombosis, partial recanalization (50.7% of the SSS remaining occluded) was accompanied by a resolution of early generalized changes of the apparent diffusion coefficient and of T2 relaxation time, indicating edema of the entire brain parenchyma. Compared with sham-treated animals, clinical skills in the experimental group improved over time, which was statistically independent from the degree of recanalization. Histopathological analysis revealed no signs of cerebral infarction.
Conclusion: This is the first animal model of SSS thrombosis that offers the possibility to investigate pathophysiological aspects of the disease as well as the influence of therapy on the nature of disease progression.