Affiliation:
1. Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark
2. Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, USA
Abstract
Brain harbors a unique ability to, figuratively speaking, shift its gears. During wakefulness, the brain is geared fully towards processing information and behaving, while homeostatic functions predominate during sleep. The blood-brain barrier establishes a stable environment that is optimal for neuronal function, yet the barrier imposes a physiological problem; transcapillary filtration that forms extracellular fluid in other organs is reduced to a minimum in brain. Consequently, the brain depends on a special fluid (the cerebrospinal fluid; CSF) that is flushed into brain along the unique perivascular spaces created by astrocytic vascular endfeet. We describe this pathway, coined the term glymphatic system, based on its dependency on astrocytic vascular endfeet and their adluminal expression of AQP4 water channels facing towards CSF-filled perivascular spaces. Glymphatic clearance of potentially harmful metabolic or protein waste products, such as amyloid-β is primarily active during sleep, when its physiological drivers, the cardiac cycle, respiration, and slow vasomotion, together efficiently propel CSF inflow along periarterial spaces. The brain's extracellular space contains an abundance of proteoglycans and hyaluronan, which provide a low-resistance hydraulic conduit that rapidly can expand and shrink during the sleep-wake cycle. We describe this unique fluid system of the brain, which meets the brain's requisites to maintain homeostasis similar to peripheral organs, considering the blood-brain-barrier and the paths for formation and egress of the CSF
Funder
Lundbeckfonden
HHS | NIH | National Institute of Neurological Disorders and Stroke
DOD | United States Army | RDECOM | Army Research Office
Fondation Leducq
Novo Nordisk
eu horizon
Publisher
American Physiological Society
Subject
Physiology (medical),Molecular Biology,Physiology,General Medicine
Cited by
251 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献