Establishing a new rat model of central venous sinus thrombosis and analyzing its pathophysiological and apoptotic changes

• Published in: Journal of neuroscience methods 2012-01, Vol.203 (1), p.130-135
• Main Authors: Yang, Hui, Meng, Zhaowei, Zhang, Chongzhi, Zhang, Peixian, Wang, Qiming
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - physiology; Cerebral venous sinus thrombosis; Disease Models, Animal; Embolism; Female; Immunohistochemistry; Rat model; Rats; Rats, Sprague-Dawley; Sinus Thrombosis, Intracranial - pathology; Sinus Thrombosis, Intracranial - physiopathology
• ISSN: 0165-0270; 1872-678X
• DOI: 10.1016/j.jneumeth.2011.09.028

► Cerebral venous sinus thrombosis (CVST) is a distinct cerebrovascular disorder, the mortality of which varies between 5.5% and 30%. ► Although much attention has been directed towards the rising incidence and variable clinical presentations of CVST in recent years, its precise pathological mechanism remain elusive. ► Animal models are indispensable for the investigation; nevertheless, many of the above models had inherent limitations, and no prior research has been focusing on the studies of apoptotic changes after CVST. ► In this research, a rat CVST model of inserting a solid plastic graft into the superior sagittal sinus was established, which was reproducible and reliable. ► We found that apoptosis played a crucial role during the development of CVST pathophysiology, which has never been reported before. This study aims to establish a new animal model of cerebral venous sinus thrombosis (CVST) and to investigate the pathophysiological and apoptotic changes of CVST. Fifty-eight adult Sprague–Dawley rats were used in the present study. They were randomized into three groups, namely control (n=6), embolism (n=26) and sham-operated (n=26) groups. In the embolism group, a self-made plastic graft was inserted in the superior sagittal sinus of each rat during the operation. Each plastic graft had a total length of 0.4cm, its conical anterior segment had the largest diameter of 0.12cm and its posterior segment became gradually thin and flat with a width of 0.2cm and length of 0.1cm. In both the embolism and the sham-operation groups, the rat brains were resected at 6h, 1, 3, and 5 days post-surgery. Gross observation and water content of samples were assessed. Immunohistochemistry for caspase 3, Bcl-2 and Bax were also performed. In the embolism group, cerebral edema reached a peak level at 6h after surgery and then gradually recovered. Significant elevated positive rates of caspase 3, Bcl-2 and Bax after embolism operation were observed, reaching peaks at 1 day time point. Yet, Bcl-2/Bax decrease significantly during the follow-up, indicating apoptosis induction in embolism operation group. The new rat CVST model made by inserting a solid graft into the superior sagittal sinus is reproducible and reliable. Apoptosis plays a crucial role during the development of CVST pathophysiology.