A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules Researchers have identified a lymphatic vessel network in the dura mater of the mouse brain, which drains cerebrospinal fluid (CSF) and brain interstitial fluid (ISF) via the glymphatic system. These vessels transport fluid into deep cervical lymph nodes (dcLNs) through foramina at the base of the skull. In a transgenic mouse model with complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was reduced, and transport from the subarachnoid space into dcLNs was blocked. However, brain ISF pressure and water content remained unaffected. These findings suggest that the mechanism of CSF flow into dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. The study also highlights the importance of the lymphatic system in CNS physiology and disease. The dural lymphatic vessels are lined by terminally differentiated lymphatic endothelium and are present in the dura mater of the CNS. These vessels drain brain ISF into dcLNs and are involved in the clearance of macromolecules from the brain. The absence of dural lymphatic vessels in K14-VEGFR3-Ig mice resulted in impaired clearance of macromolecules from the brain. The study also shows that the dural lymphatic vessels are likely to represent the most important CSF source for the extracranial lymph compartment. The findings open new avenues for research on the role of dural lymphatic vessels in the trafficking of cerebral immune cells, antigen presentation in dcLNs, and the clearance of brain edema. The study also suggests that the absence of dural lymphatic vessels may explain why primary brain tumors rarely metastasize into cervical lymph nodes. The study has important implications for understanding the mechanisms of brain waste management in diseases such as Alzheimer's disease.A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules Researchers have identified a lymphatic vessel network in the dura mater of the mouse brain, which drains cerebrospinal fluid (CSF) and brain interstitial fluid (ISF) via the glymphatic system. These vessels transport fluid into deep cervical lymph nodes (dcLNs) through foramina at the base of the skull. In a transgenic mouse model with complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was reduced, and transport from the subarachnoid space into dcLNs was blocked. However, brain ISF pressure and water content remained unaffected. These findings suggest that the mechanism of CSF flow into dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. The study also highlights the importance of the lymphatic system in CNS physiology and disease. The dural lymphatic vessels are lined by terminally differentiated lymphatic endothelium and are present in the dura mater of the CNS. These vessels drain brain ISF into dcLNs and are involved in the clearance of macromolecules from the brain. The absence of dural lymphatic vessels in K14-VEGFR3-Ig mice resulted in impaired clearance of macromolecules from the brain. The study also shows that the dural lymphatic vessels are likely to represent the most important CSF source for the extracranial lymph compartment. The findings open new avenues for research on the role of dural lymphatic vessels in the trafficking of cerebral immune cells, antigen presentation in dcLNs, and the clearance of brain edema. The study also suggests that the absence of dural lymphatic vessels may explain why primary brain tumors rarely metastasize into cervical lymph nodes. The study has important implications for understanding the mechanisms of brain waste management in diseases such as Alzheimer's disease.