A network of vessels in mice has been found to connect the brain with the body’s lymphatic system. This discovery suggests the existence of an overlooked brain drainage system that is crucial for maintaining the health and function of the central nervous system. If this finding applies to humans, it could significantly alter our understanding of fluid circulation that supports the brain and spinal cord. Cerebrospinal fluid (CSF) is a clear liquid responsible for carrying nutrients to the central nervous system, regulating fluid balance, and removing waste products from brain tissue. In humans, CSF is constantly drained and replaced, a process that occurs three to five times a day. The rate of this clearance can decrease with age and is associated with sleep quality and cognitive function. Understanding the circulation of CSF is vital for understanding human health and disease, yet there is still uncertainty regarding the ultimate destination of this fluid once the brain is finished with it. For many years, it was believed that CSF was drained through specialized veins surrounding the brain and spinal cord. However, recent evidence suggests that this may not be the case. Instead, it is possible that CSF drains through the body’s lymph nodes. A new study led by researchers at South Korea’s Institute for Basic Science and the University of Missouri has identified a previously unknown route that transports CSF from the brain to lymph nodes located in the neck. The international team of researchers discovered a unique network of lymphatic vessels near the top part of the throat in mice, just behind their nose, a structure that had not been clearly identified before. By injecting fluorescent markers into the brain tissue of rodents and live mice, the researchers were able to map a network known as the nasopharyngeal lymphatic plexus, indicating that it plays a significant role in the drainage of CSF. These findings support previous brain imaging data from 2022, which showed that CSF drainage in mice occurs through lymphatics located in the nasopharynx. In a review for Nature, Irene Spera and Steven Proulx, physiologists from the University of Bern, praised the recent discovery. As authors of studies suggesting the possibility of such a “secret passage,” they believe that the results provide “indisputable evidence that, at least in mice, the nasopharyngeal lymphatic plexus is critically involved in CNS clearance.” Additionally, the researchers found a similar structure in the brains of crab-eating macaques, indicating that this lymphatic plexus is not exclusive to mice. Although they did not witness the drainage process in action as they did in mice, the findings among primates suggest that this pathway is conserved across various mammalian species. The discovery could have important implications for the understanding and treatment of conditions related to impaired CSF drainage, such as in human neurodegenerative disorders like Alzheimer’s disease, where waste products tend to accumulate in the brain. The researchers observed that the nasopharyngeal lymphatic plexus shrinks with age in mice and becomes less effective at clearing CSF. They were able to enhance the function of these deteriorating vessels by stimulating them with a growth factor protein, hinting at a potential target for neurodegenerative treatment. Some recent evidence suggests that CSF may drain into the nasal cavity at the top of the throat via cranial nerves in humans. However, the exact mechanism of how CSF drains from the nasal cavity to lymph nodes in the neck remains unclear. The researchers propose a compelling explanation based on their findings from rodents and monkeys, suggesting that the human nasopharyngeal plexus may resemble the structure observed in mice and monkeys. Supervisor Gou Young Koh from the Institute for Basic Science states, “We plan to verify all the findings from the mice in primates, including monkeys and humans. We aim to investigate in a reliable animal model whether activating the cervical lymphatic vessels through pharmacological or mechanical means can prevent the exacerbation of Alzheimer’s disease progression by improving CSF clearance.” The study was published in Nature.
