Cerebral venous blood flow regulates brain fluid homeostasis and neuro-immune surveillance

Lymphatic vessels and veins are closely associated in the dura mater around the venous sinuses, but how much venous outflow can influence the structure and function of dural lymphatics remains unknown. To investigate this vein-lymphatic interaction we developed a mouse model of cerebral venous outflow obstruction. Using postmortem and live imaging, we observed that glymphatic-lymphatic coupling is depending on venous drainage from the cranium and that lymphatic drainage impairment arises under conditions of venous drainage dysfunction. Long-lasting immune cell recruitment was also observed in the dura-mater of mice with venous outflow obstruction and associated with a transient alteration of vigilance behavior. This preclinical work was combined with clinical research on patients with Idiopathic intracranial hypertension (IIH), a disease characterized by cerebral venous outflow obstruction, brain fluid retention, leading to intracranial hypertension, headaches, and cognitive dysfunctions. Magnetic resonance-lymphatic imaging was used to explore lymphatic vasculature and brain fluid circulation in patients with IIH compared to controls, allowing us to correlate cerebral venous system dysfunction with dysregulation of CSF clearance and lymphatic drainage. Altogether, these data demonstrate functional coupling of cerebral venous flow and glymphatic-lymphatic brain fluid drainage, which is conserved between mice and humans.