A Rabbit Model Of Cerebral Venous Sinus Thrombosis Established By Ferric Chloride And Thrombin Injection

Background and Objectives:Cerebral venous sinus thrombosis is a rare type of ischemic cerebrovascular disease,the morbidity of CVST increased year by year that accounting for 1%of all stroke.All age groups can be affected,but the age of onset is mostly concentrated in young people aged 20-30 years.The epidemic factors inculde intracranial infection,oral contraceptives,pregnancy,postpartum.CVST patients often present signs and symptoms of elevated intracranial pressure and focal deficits.Because of its complex etiology and various clinical manifestations lead to its misdiagnosis and high mortality,the general case fatality rate reaches 4.39%,but the mortality rate may increase to 53%when the patient has encephalopathy or acute encephalopathy.In the research field of cerebral venous sinus thrombosis,since animal models can shorten the study time,at the same time,animal models can creat fixed position thrombosis and pathological changes under conditions of artificially controlled variable factors,so the animal model can be used to study the occurrence,development,biological characteristics,and treatment of the diseases.The establishment of animal models has become an indispensable tool for simulating the progress and pathological changes of human venous sinus thrombosis.Therefore,the establishment of an animal model that should consistent with the pathological changes of clinical venous sinus thrombosis with stability and high reproducibility is the key to promote the prevention and treatment of venous sinus thrombosis in the future.In this experiment,we have employed an animal model that the superior sagittal sinus was attached with 40%of ferric chloride and combined with thrombin injection forthermore evaluated the feasibility and application value of the model.Methods:120 healthy rabbits were randomly divided into four groups,including sham-operated group?n=30?,Fecl₃ group?n=30?,Fecl₃+thrombin?T?group?n=30?,and thrombin?T?group?n=30?.A 2.0 cm×1.2 cm cranial window between Lambda and Bregma was created,in sham-operated animals,a 2.0 cm×0.2 cm surgical cotton piece imbibed with normal saline was placed in the SSS for 10 min.In the Fecl₃group,cotton pieces with 40%Fecl₃ were used instead of 0.9%saline in the exposed SSS.After 10 min,the cotton piece was removed,and the field was flushed with normal saline several,in the Fecl3+T group,cotton pieces with 40%Fecl3 were applied;after 5 min,the cotton was removed and a micro-dose injector was inserted into the SSS from the rostral to caudal direction.Then,thrombin was injected slowly into the SSS for 5 min.In the T group,only thrombin was injected into the SSS for 10min.Digital subtraction angiography?DSA?was performed to ensure thrombosis and evaluate the recanalization rate 7 days post-CVST.Neurological evaluation,Evans blue injection,2,3,5-Tripheny-ltetrazolium chloride?TTC?,and hematoxylin-eosin?H&E?staining were used to assess thrombosis and the accompanying brain parenchyma.Results:No animal died spontaneously during the study period,except one model in the T group with severe subdural bleeding.The Fecl₃ and Fecl₃+T groups were all established thrombosis of SSS,in the T group,however,the sinus thrombosis was showed in 26/29 animals.The thrombus recanalization was 70%in Fecl₃ group and10%in Fecl₃+T group and 20%in T group.Brain infarction,hemorrhage,cell edema,and disruption of the blood-brain barrier?BBB?were also observed in Fecl₃+T group.Conclusion:The method of inducing cerebral venous sinus thrombosis by applying 40%FeCl₃ and injecting thrombin is feasible and efficient.This experimental model mimics the pathogenesis and pathophysiology of actual CVST.