Outflow of cerebrospinal fluid is predominantly through lymphatic vessels in mice

Steven T. Proulx,Ph.D., Qiaoli Ma, Miriam Ries and Michael Detmar


Senior Scientist / Group Leader, Institute of Pharmaceutical Sciences, ETH Zürich, Zürich, Switzerland



Cerebrospinal fluid (CSF) has been commonly accepted to drain through arachnoid projections from the subarachnoid space to the dural venous sinuses. However, a lymphatic component to CSF outflow has long been known. Here, we utilized lymphatic-reporter mice and high-resolution stereomicroscopy to characterize the anatomical routes and dynamics of outflow of CSF. Tracers rapidly reached lymph nodes using perineural routes through foramina in the skull and at the caudal end of the spine. Using noninvasive imaging techniques that can quantify the transport of tracers to the blood and lymph nodes, we found that lymphatic vessels are the major CSF outflow pathway for both large and small molecular tracers in mice. A significant decline in CSF lymphatic outflow was found in aged compared to young mice, suggesting that the lymphatic system may represent a target for age-associated neurological conditions.