The Regulation of Cerebral Spinal Fluid Flow and Its Relevance to the Glymphatic System
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(2020) 20:58
DEMENTIA (K.S. MARDER, SECTION EDITOR)
The Regulation of Cerebral Spinal Fluid Flow and Its Relevance to the Glymphatic System Colin D. McKnight 1 & Renee M. Rouleau 2 & Manus J. Donahue 1,2,3 & Daniel O. Claassen 2 Accepted: 25 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review The glymphatic system is a relatively new concept that has been associated with regulation of cerebrospinal fluid (CSF), as well as brain waste clearance. Novel techniques to study glymphatic dysfunction have in turn prompted a reassessment of brain physiology and underlying elements of neurological disease. This review incorporates a contemporary imaging perspective focused on understanding the regulation of CSF flow, thus expanding the putative clinical relevance of this system and the relationships between CSF flow and glymphatic function. Recent Findings MR imaging studies, especially those that employ intrathecal gadolinium contrast, have identified potentially new pathways regulating CSF production, absorption, and clearance. These studies, when viewed in the context of more historical anatomic descriptors of CSF production and absorption, provide a more robust description of CSF physiology and waste clearance. Summary CSF production and resorption are under-investigated and could be related to various pathophysiologic processes in neurodegeneration. Anatomically based clinical exemplars of CSF clearance are discussed. Future studies should focus on linking glymphatic functionality with neurological disease. Keywords Glymphatic . Neuroimaging . Neurodegeneration . Arachnoid granulations . Perivascular space
Introduction The suggestion of a glymphatic system in 2012 has resulted in a reinvigorated discussion regarding the regulation of cerebrospinal fluid (CSF) flow, production, and clearance [1]. Glymphatic flow, as assessed in animal models, appears organized and modulated via functional states during which this system is most active (i.e., sleep) [2]. This organized CSF flow occurs through perivascular spaces and within the brain parenchymal interstitium and is regulated by aquaporin 4 channels. Multiple animal models have demonstrated fluid flow This article is part of the Topical Collection on Dementia * Daniel O. Claassen [email protected] 1
Department of Radiology, Vanderbilt University Medical Center, Nashville, TN, USA
2
Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA
3
Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN, USA
from subarachnoid, to periarterial space, where it subsequently enters the interstitial compartment as regulated by the aquaporin 4 channel. Along the efferent end of this system, aquaporin 4 channels allow for passage of fluid from the interstitial space to the perivenular space from which point the fluid again travels to the subarachnoid compartment. Animal studies have provided key insights into the putative clinical significance of this system with regar
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