Lymphatic Vessels Gain Access to Cerebrospinal Fluid Through Unique Association with Olfactory Nerves

Background: Physiological studies suggest that a major portion of cerebrospinal fluid (CSF) drainage is associated with transport along cranial and spinal nerves with absorption taking place into lymphatic vessels external to the central nervous system. Especially important is CSF transport through the cribriform plate in association with the olfactory nerves. This study examined the anatomical connections that link the CSF and extracranial lymphatics at the base of the brain. Methods and Results: The contrast agent, Yellow Microfil, was infused into the cranial subarachnoid compartment of 2- to 7-day-old lambs postmortem. In some animals, blue Microfil was perfused into the carotid arteries. Yellow Microfil was observed in extensive lymphatic networks in the submucosa associated with the olfactory and respiratory epithelium. Since little of the contrast agent was present within the interstitium of the olfactory submucosa, there appeared to be direct continuity between the subarachnoid space, the perineurial spaces of the olfactory nerve fibers that penetrated the cribriform plate, and the lumens of the lymphatic vessels within the olfactory submucosa. Lymphatics encircled the olfactory nerves at the level of the emerging nerve rootlets (in many cases providing the outer limit of the perineurial space) and then dispersed freely in the submucosa at greater distance from the cribriform plate. These vessels converged into larger collecting ducts that emptied into various lymph nodes in the head and neck. Conclusions: Lymphatic vessels gain access to the brain extracellular fluid (CSF) in an unusual anatomical association with the olfactory nerves external to the cranial vault. This study highlights the important role played by lymphatic vessels in CSF absorption.