Murine Model of Cerebral Venous Outflow Occlusion Through Bilateral Ligation of Jugular Veins

Lymphatic vessels play a key role in maintaining fluid homeostasis and immune surveillance within tissues. At the brain's border, the dural meninges contain lymphatic vessels closely neighboring venous sinuses. In humans, idiopathic intracranial hypertension (IIH) is associated with stenosis of dural venous sinuses, suggesting that venous outflow disturbances may affect brain fluid regulation and meningeal lymphatic drainage. To explore this relationship in a controlled setting, we developed a mouse model of cerebral venous outflow occlusion via bilateral ligation of both internal and external jugular veins (JVL). This surgical protocol is reproducible, not invasive, and achieves a high success rate (98.4%) with expected postoperative signs such as facial and brain swelling as well as extracranial vascular remodeling. Two-dimensional time-of-flight (2D-TOF) MR venography followed by three-dimensional (3D) reconstruction confirmed upstream venous congestion. This model enables the longitudinal study of the consequences of impaired cerebral venous outflow on cerebrovascular architecture, lymphatic remodeling, and brain fluid clearance. By manipulating the vessels at the neck, JVL allows investigation of these processes without damaging intracranial structures. Despite anatomical differences between species, JVL provides a robust and accessible approach to dissect the interplay between venous outflow, lymphatic drainage, and fluid homeostasis in the brain.