Cerebral venous blood flow regulates intracerebral pressure and brain clearance via meningeal lymphatic vessels

Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure and dural venous sinus stenoses, which can be relieved by venous stenting. Here we investigated whether venous blood flow may play a role in controlling brain pressure. Using magnetic resonance imaging in patients with IIH and healthy controls, we identified that dural venous stenoses in IIH were associated with alterations of the perivenous fluid pattern and brain edema. We developed a mouse model of jugular vein ligation (JVL), which developed transient intracerebral hypertension, brain edema and impaired brain clearance, along with defective meningeal lymphatic vessels (MLVs). MLV depletion increased intracerebral pressure in control and JVL mice, but only MLV-deficient ligated mice failed to restore brain fluid clearance. These findings implicate MLVs in the control of intracerebral pressure and establish the dural venous sinuses as critical platforms where venous flow directs MLVs to ensure brain fluid clearance. The authors show that cerebral venous blood flow and meningeal lymphatics co-regulate intracranial pressure and brain clearance in mice and humans. This finding supports idiopathic intracranial hypertension as a cerebral venous disorder.