The brain and the lymphatic system

The brain lacks a local lymphatic system, primarily due to the closed environment of the skull which sets strict requirements for control of fluid balance and intracranial pressure. Proper fluid and pressure balance are maintained in the brain through the unique systems of cerebrospinal and interstitial fluid as well as a tight coupling between these systems and the surrounding lymphatic drainage pathways, primarily in the cervical lymph nodes. In this chapter, we will review the physiology of cerebrospinal and interstitial fluid, provide an overview of their primary production and drainage mechanisms, and discuss the still-debated issue of the interconnections of these systems and their relevance to human physiology. We present the current evidence pointing to the importance of the extracranial lymphatic system as one of the key drainage pathways for cerebrospinal fluid from the brain, and conclude with the implications of these interconnected pathways to the ongoing revision for the concept of immune privilege of the brain.