Cerebral venous thrombosis (CVT) is a rare type of venous thromboembolism (VTE). It is an important cause of stroke in young adults and children. Severe CVT, which is characterized by cerebral venous infarction or hemorrhage, seizures, or disturbance of consciousness, has more severe clinical manifestations and a worse prognosis. It is commonly believed that the onset of severe CVT gave credit to venous return disorder, with the underlying pathogenesis remaining unclear. There is increasing evidence suggesting that an inflammatory response is closely associated with the pathophysiology of severe CVT. Preclinical studies have identified the components of neuroinflammation, including microglia, astrocytes, and neutrophils. After CVT occurrence, microglia are activated and secrete cytokines (e.g., interleukin-1β and tumor necrosis factor-α), which result in a series of brain injuries, including blood-brain barrier disruption, brain edema, and cerebral venous infarction. Additionally, astrocytes are activated at the initial CVT stage and may interact with microglia to exacerbate the inflammatory response. The extent of cerebral edema and neutrophil recruitment increases temporally in the acute phase. Further, there are also changes in the morphology of inflammatory cells, expression of inflammatory mediators, and inflammatory pathway molecules with CVT progression. Lately, some clinical research suggested that some inflammation-related biomarkers are of great value in assessing the course, severity, and prognosis of severe CVT. Moreover, basic and clinical research suggested that anti-inflammatory therapy might hold promise in severe CVT. This study reviews the current literature regarding the involvement of inflammation in the pathophysiology and anti-inflammatory interventions of severe CVT, which would contribute to informing the pathophysiology mechanism and laying a foundation for exploring novel severe CVT therapeutic strategies.

Aims An applicable cerebral venous sinus thrombosis (CVST) model is imperative for exploring its pathophysiology. We established a novel severe CVST model using semi‐ligation, ferric chloride, and thrombin. Methods A total of 138 male Sprague–Dawley rats were randomly divided into semi‐ligation (n = 75) and non‐semi‐ligation (n = 63) groups. A sham group (n = 46) was also included. We compared short‐term and long‐term neurological and cognitive dysfunction, mortality rates, thrombus load, venous infarction volume, the blood–brain barrier permeability, brain water content, and microglia activation among the three groups. Results Thrombi involving multiple venous sinuses appeared in all semi‐ligation rats within 2 days postoperatively. Compared with the non‐semi‐ligation group, short‐term and long‐term neurological dysfunction were more severe (p < 0.05), and thrombus weight, venous infarction volumes, and microglia activation were more significant (p < 0.05) in the semi‐ligation group. Further, the cognitive function of the semi‐ligation group significantly decreased (p < 0.05) on postoperative day 21. Cumulative mortality rates between the semi‐ligation and non‐semi‐ligation groups did not differ significantly. Conclusion Semi‐ligation combined with ferric chloride and thrombin can produce a severe CVST model with multiple venous sinus involvement, which is suitable for short‐ and long‐term neurological and cognitive dysfunction assessment.