Lymphatic Drainage System of the Brain: a New Player in Neuroscience

The lymphatic system not only plays an important role as a drainage eliminating metabolic wastes and toxins from tissues, but also represents an arena for the unfolding of immune response scenarios aimed at protecting the organism from bacteria and viruses. In the central nervous system (CNS), drainage processes proceed with the same intensity as in peripheral tissues. The brain actively exchanges nutrients with the blood and excretes metabolic waste products through the drainage routes closely related to the peripheral lymphatic system. The same routes allow the traffic of immune cells and antibodies to the CNS, thus providing a communication between the peripheral and central immune systems. Over the bicentennial history of brain drainage studies, a lot of facts have been accumulated to suggest indirectly the presence of lymphatic vessels in the CNS. However, even with the advent of high-tech imaging of brain structures and a rediscovery of the meningeal lymphatic vessels (MLVs), which was a watershed in neuroscience, scientists have not advanced beyond confirming the already existing dogma that the lymphatic network is present exclusively in the brain meninges, but not in brain tissues. In fact, however, the rediscovery of MLVs by American scientists was not a “true revelation”, as they were first described by the Italian anatomist Mascagni two centuries earlier, and his results were confirmed later on in many other studies performed on the meninges in humans, macaques, rodents, dogs, rabbits and zebrafish. As a result, the scientific community did not recognize the “forgotten” MLVs as a new discovery. This review highlights the turning points that occurred in neuroscience when a new player has entered the game and orchestrated innumerable efforts of scientists to explain how unnecessary molecules and toxins are removed from the brain, as well as how drainage and immunity are implemented in the CNS. This is an important informational and creative platform both for new fundamental knowledge about the lymphatic system in the brain, as well as for the development of innovative neurorehabilitation technologies based on the management of lymphatic drainage processes.