Novel Rat Model of Severe Cerebral Venous Sinus Thrombosis Established by Combination of Semi-Ligation, Ferric Chloride, and Thrombin.

Abstract

Cerebral venous sinus thrombosis (CVST) is a distinct type of stroke that predominantly affects young individuals, particularly pregnant women. Approximately 60% of CVST patients develop venous cerebral infarction or hemorrhage, which is defined as severe CVST. Currently, various methods are employed both domestically and internationally to induce CVST in animal models. However, these models fail to fully replicate the pathophysiological mechanisms underlying severe CVST, thereby limiting basic research on this condition. A novel rat model of severe CVST can be established through semi-ligation in combination with ferric chloride and thrombin. Semi-ligation was achieved by measuring the cerebral blood flow (CBF) in the region of interest (ROI) before and after ligation of the superior sagittal sinus (SSS) using a Perfusion Speckle Imager (PSI). Semi-ligation of the SSS induces blood stasis within the venous sinus. The topical application of ferric chloride on the surface of the SSS leads to endothelial injury, while direct injection of thrombin into the sinus creates a localized hypercoagulable state. This approach effectively mimics the three key components of thrombosis formation: stasis, endothelial damage, and hypercoagulability. The resulting model exhibits a substantial thrombotic burden involving multiple venous sinuses simultaneously. The induced thrombus remains stable for at least 1 week. The 2,3,5-triphenyltetrazolium chloride (TTC) staining demonstrates that this model can consistently produce large-area venous cerebral infarction, which persists for up to 7 days. This model can even induce epileptic seizures in rats, a capability that previous models were unable to achieve. The disruption of the blood-brain barrier was observed using Evans blue (EB) staining. Therefore, the severe CVST model established through semi-ligation combined with ferric chloride and thrombin administration more accurately replicates the pathophysiological progression of severe CVST in humans, demonstrating stability and reliability.