The Glymphatic System
- brain-wide waste clearance
Despite a high level of metabolic activity, the brain does not have a conventional lymphatic system to remove metabolites. The glia-lymphatic (glymphatic) system is a waste removal system that uses the perivascular space of the brain for fluid transport. The glymphatic system is a bulk flow system driven arterial pulsation and results in convective flow in the perivascular spaces. The glymphatic system is most active in the sleep state, where production of cerebrospinal fluid (CSF) is highest and the interstitial space is larger. Solutes as well as peptides such as amyloid beta can be transported in perivascular pathways by the glymphatic system and eliminated to the lymphatic vessels. Accumulation of proteins, such as amyloid beta, is a common feature of neurodegenerative diseases and we believe that the control of the glymphatic system could prevent or curb neurodegenerative diseases. Due to the recent discovery of the glymphatic system, many new discoveries are waiting to be made, including how to effectively manipulate the glymphatic system.
Astrocytes are the key regulators of brain homeostasis. Their endfeet processes ensheath the cerebral vasculature and contact thousands of synapses. We are interested in the endfeet of astrocytes, as they form perivascular pathways used by the glymphatic system for fluid transport. Aquaporin 4 (AQP4) water channels in the astrocyte endfeet are crucial for influx of cerebrospinal fluid (CSF) into the brain and clearance of solutes. Besides AQP4 molecular drivers of glymphatic flow remain elusive.
Similar to the lymphatic system, the glymphatic system connects to lymph nodes in the cervical region. Thus, there is a strong association between glymphatic and immune function. Fluid drains from the brain into meningeal lymphatic vessels, to the nasal mucosa via the cribriform plate, via spinal and cranial nerves, or simply perivenously. Drainage from the brain will mount an immune response in cervical lymph nodes. The idea of the brain being ‘immune privileged’ remains true in the sense that there are much fewer patrolling T cells in the brain e.g. than in the skin. However, meningeal lymphatic vessels and CSF efflux to cervical lymph via the nasal mucosa is understudied in relation to central nervous system immune function.