Pathways of Fluid Drainage from the Brain ‐ Morphological Aspects and Immunological Significance in Rat and Man

There is firm physiological evidence for the lymphatic drainage of interstitial fluid and cerebrospinal fluid from the brains of rats, rabbits and cats. The object of this review, is to describe firstly the morphological aspects of lymphatic drainage pathways from the rat brain and secondly, to explore through scanning and transmission electron microscope techniques, the possibility of similar lymphatic drainage pathways in man. Interstitial and oedema fluid spreads diffusely through the white matter in the rat and appears to drain into the ventricular cerebrospinal fluid. In grey matter, however, tracers pass along perivascular spaces to the surface of the brain and into the cerebrospinal fluid. Paravascular compartments in the subarachnoid space follow the course of major arterial branches to the circle of Willis and thence along the ethmoidal arteries to the cribriform plate of the ethmoid bone. Particulate tracers, such as Indian ink, enter channels in the arachnoid beneath the olfactory bulbs and connect directly with nasal lymphatics through channels which pass through holes in the cribriform plate. Proteins and other solutes may also drain along other cranial nerves. Thus, there is a bulk flow pathway for interstitial and cerebrospinal fluid from the rat brain into cervical lymphatics. In man, it is probable that diffuse interstitial drainage of fluid from the white matter occurs in a similar way to that in the rat. Furthermore, the anatomical pathways exist by which bulk drainage of fluid could occur along perivascular spaces from the grey matter into perivascular spaces of the leptomeningeal arteries and thence into the cerebrospinal fluid (CSF). Compartmentalisation of the subarachnoid space may allow directional flow of CSF to occur. Thus, although the vast bulk of CSF in man drains through arachnoid villi and granulations, anatomical pathways exist by which selective flow for lymphatic drainage of brain interstitial fluid and inflammatory cells could occur. Physiological evidence for traffic along such pathways in man, however, is still sparse. It seems probable that any lymphatic drainage of CSF in man is overshadowed by the high volume passage of CSF through the arachnoid granulations and villi.