Lumped Parameter Simulations of Lymphatic Vessels Reveal Dynamics of Cerebrospinal Fluid Efflux from the Skull

Experiments from the last decade have revealed that lymphatic vessels exist in the meninges (the tissue surrounding the brain) and play an important role in removing metabolic waste from the brain. Cerebrospinal fluid (CSF) circulates through the brain (known as the glymphatic system) carrying the wastes then drains through these meningeal lymphatic vessels (MLVs) in many different locations, eventually reaching the larger cervical lymphatic vessels (CLVs) located in the neck. The details of these different parallel outflow routes are still debated, but recent studies in mice suggest that the majority of CSF leaves across the cribriform plate, which is in the vicinity of the nasal sinuses. Our research aims to simulate this efflux pathway to gain insight into the driving mechanisms of efflux and variability in physiological and pathological conditions. We adapt prior lumped numerical modeling to simulate CLVs, which we connect to a network of channels representing MLVs that drain fluid from a variable-pressure compartment representing the subarachnoid space inside the skull. We investigate how the intrinsic pumping (i.e., contractions) of CLVs and oscillations of intracranial pressure affect the net flow. Our preliminary results provide insight into brain metabolic waste removal via CSF efflux and point to mechanisms of disrupted clearance in pathological conditions, increasing the risk of developing neurodegenerative diseases.