A Novel Rat Model for Cerebral Venous Sinus Thrombosis Matched Clinical Syndrome: Combination of Clinical Cases and Experimental Validation

Abstract

BackgroundCerebral venous sinus thrombosis (CVST) is a rare neurovascular disorder with highly variable manifestations and clinical course. To investigate its pathophysiology, an animal model with a properly matched clinic is needed. MethodsThis study consisted of clinical and animal studies. In the clinical section, eligible patients with CVST and healthy controls’ detailed data were recorded between January 1, 2016 and May 31, 2021. For the animal section, a novel rat model of CVST was established by inserting a water-swellable rubber into the superior sagittal sinus and applying imaging, histopathological, serological and behavioral tests to investigate the corresponding pathophysiological changes. A total of 19 CVST patients and 25 healthy controls were enrolled, and the data demonstrated the typical characteristics of venous infarction with elevated intracranial pressure, vasogenic edema, and secondary hemorrhage. A total of 80 rats were randomly divided into two groups: sham group (n = 40) and model group (n = 40). ResultsThe imaging results showed consistent characteristics of brain injury and venous morphology in the animal models and CVST patients. Histological and serological findings further illustrated the predominance of vasogenic edema as pathological change, while behavioral tests revealed anxiety and depression in model rats. ConclusionsWe established a novel CVST rat model with reproducible surgical methods and stabilization of pathological changes, and compared it to retrospective CVST patient data, proving that the model could almost reproduce the clinical syndromes. This model provides reliable support for the study of CVST pathophysiology and the evaluation of therapies.