Abstract
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 utilize lymphatic-reporter mice and high-resolution stereomicroscopy to characterize the anatomical routes and dynamics of outflow of CSF. After infusion into a lateral ventricle, tracers spread into the paravascular spaces of the pia mater and cortex of the brain. Tracers also rapidly reach lymph nodes using perineural routes through foramina in the skull. Using noninvasive imaging techniques that can quantify the transport of tracers to the blood and lymph nodes, we find that lymphatic vessels are the major outflow pathway for both large and small molecular tracers in mice. A significant decline in CSF lymphatic outflow is found in aged compared to young mice, suggesting that the lymphatic system may represent a target for age-associated neurological conditions.
Highlights
Cerebrospinal fluid (CSF) has been commonly accepted to drain through arachnoid projections from the subarachnoid space to the dural venous sinuses
We find that the major outflow pathway from CSF for both large and small molecular tracers in mice is through perineural routes to reach the lymphatic system
Dynamic imaging suggested that lymphatic outflow was the major outflow route for CSF rather than venous routes, with even small molecular tracers not demonstrating immediate blood uptake
Summary
Cerebrospinal fluid (CSF) has been commonly accepted to drain through arachnoid projections from the subarachnoid space to the dural venous sinuses. The outflow pathways were defined using tracers to be within sheaths around cranial nerves, with the cribriform plate route along olfactory nerves that extends to lymphatic vessels in the nasal mucosa deemed especially important[17,20,21] These sheaths enclose extensions of the SAS that project extracranially with the nerves through foramina of the skull. Two recent reports in mice have indicated that the dura mater of the CNS is endowed with a network of lymphatic vessels capable of draining CSF or brain ISF30,31 This potential route for drainage of CSF is controversial in light of the existence of the arachnoid barrier layer between the SAS and the dura mater[4]. As many neurological conditions are associated with the aging process, it is critical to determine if lymphatic outflow of CSF is altered in aged conditions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
