Cognitive Brain Science: Glymphatic (Lymphatic) System, Circadian Stress and Chronic Insomnia

Abstract

Sleep evolutionarily persists in all species, and sleep disturbance is the general pathogenesis of neurodegeneration, circadian stress, and electromagnetic load/overload. Sleep quality in human decreases with age, and disruption of normal sleep architecture often precedes the onset of neurodegenerative diseases. The lymphatic system, which cleans the brain of protein waste, is mostly active during sleep. Chronic stress remodels and restructures the lymphatic vasculature. The glymphatic system because of its dependence on glial cells — non-neuronal cells in the central nervous system (CNS) that do not produce electrical impulses but support and protect neurons. The present and functional lymphatic vascular system is found in the meninges that cover the central CNS. This unexpected (rediscovery) discovery led to a reassessment of fluid and solute drainage mechanisms in the CNS, neuroimmune interactions, and the involvement of meningeal lymph nodes in the onset and progression of neurological disorders. Various factors affecting meningeal lymphatic function, such as growth factor signaling and aging, and their effect on the continuous flow of brain-derived molecules and meningeal immune cells to the cervical lymph nodes. Discovery of the role of the lymphatic vasculature draining the CNS in various pathologies that have a strong neuroinflammatory component, including brain injuries, tumors and aging-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Neural networks that link sleep, aging, lymphatic system clearance and protein aggregation have shed new light on the pathogenesis of a wide range of neurodegenerative diseases for which lymphatic system failure may represent a therapeutically targeted end-to-end common pathway.