Cleaning the sleeping brain – the potential restorative function of the glymphatic system

Hauglund, Natalie L.; Pavan, Chiara

doi:10.1016/j.cophys.2019.10.020

Cited by 83 publications

(52 citation statements)

References 49 publications

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“…Several lines of evidence documented that β-amyloid and tau exit the brain via the glymphatic system, and glymphatic activity and CSF outflow decrease significantly in old mice ( Iliff et al, 2014 ; Kress et al, 2014 ; Jessen et al, 2015 ; Ma et al, 2017 ). The glymphatic system removes potentially harmful metabolites from the CNS especially during sleep ( Rasmussen et al, 2018 ; Hauglund et al, 2020 ). Accordingly, in animal models it was observed that during natural sleep or anaesthesia there is an enlargement of the interstitial space, which increases convective CSF exchange with ISF, and β-amyloid clearance rate ( Xie et al, 2013 ).…”

Section: Glymphatic System and Cns Disordersmentioning

confidence: 99%

“…This is correlated with reduced slow wave activity (SWA). In fact, high SWA and certain types of anaesthesia support glymphatic activity, while norepinephrine signaling in the brain (and wakefulness, in general) has an attenuating effect ( Xie et al, 2013 ; Hablitz et al, 2019 ; Hauglund et al, 2020 ). Disrupting the SWA is enough to abolish waste clearance ( Ju et al, 2017 ), and sleep deprivation is correlated with increased levels of β-amyloid in the brain of both animals and humans ( Kang et al, 2009 ; Shokri-Kojori et al, 2018 ).…”

Section: Glymphatic System and Cns Disordersmentioning

confidence: 99%

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Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS

et al. 2021

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The classic concept of the absence of lymphatic vessels in the central nervous system (CNS), suggesting the immune privilege of the brain in spite of its high metabolic rate, was predominant until recent times. On the other hand, this idea left questioned how cerebral interstitial fluid is cleared of waste products. It was generally thought that clearance depends on cerebrospinal fluid (CSF). Not long ago, an anatomically and functionally discrete paravascular space was revised to provide a pathway for the clearance of molecules drained within the interstitial space. According to this model, CSF enters the brain parenchyma along arterial paravascular spaces. Once mixed with interstitial fluid and solutes in a process mediated by aquaporin-4, CSF exits through the extracellular space along venous paravascular spaces, thus being removed from the brain. This process includes the participation of perivascular glial cells due to a sieving effect of their end-feet. Such draining space resembles the peripheral lymphatic system, therefore, the term “glymphatic” (glial-lymphatic) pathway has been coined. Specific studies focused on the potential role of the glymphatic pathway in healthy and pathological conditions, including neurodegenerative diseases. This mainly concerns Alzheimer’s disease (AD), as well as hemorrhagic and ischemic neurovascular disorders; other acute degenerative processes, such as normal pressure hydrocephalus or traumatic brain injury are involved as well. Novel morphological and functional investigations also suggested alternative models to drain molecules through perivascular pathways, which enriched our insight of homeostatic processes within neural microenvironment. Under the light of these considerations, the present article aims to discuss recent findings and concepts on nervous lymphatic drainage and blood–brain barrier (BBB) in an attempt to understand how peripheral pathological conditions may be detrimental to the CNS, paving the way to neurodegeneration.

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Section: Glymphatic System and Cns Disordersmentioning

confidence: 99%

Section: Glymphatic System and Cns Disordersmentioning

confidence: 99%

Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS

et al. 2021

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“…This has obvious implications for brachycephalic dogs with BOAS, especially if they have sleep-disordered breathing. Intracranial pressure increases during sleep, and disordered sleep will also affect glymphatic drainage, which is more active during sleep [ 21 , 55 , 56 ].…”

Section: Effect Of Brachycephaly On Respiration and Sleepmentioning

confidence: 99%

The Need for Head Space: Brachycephaly and Cerebrospinal Fluid Disorders

Rusbridge

Knowler

2021

Life

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Brachycephalic dogs remain popular, despite the knowledge that this head conformation is associated with health problems, including airway compromise, ocular disorders, neurological disease, and other co-morbidities. There is increasing evidence that brachycephaly disrupts cerebrospinal fluid movement and absorption, predisposing ventriculomegaly, hydrocephalus, quadrigeminal cistern expansion, Chiari-like malformation, and syringomyelia. In this review, we focus on cerebrospinal fluid physiology and how this is impacted by brachycephaly, airorhynchy, and associated craniosynostosis.

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“…[37][38][39] As described by Benveniste et al, the glymphatic system may be viewed as a waste processing unit, 34,40 with the key constituents being: perivascular AQP4 water channels, hydraulic forces associated with arterial pulsation, respiratory effort, and body position, 34,[41][42][43] regular CSF production and transport, and a state of arousal. 44,45 The convoluted nature of the glymphatic system along with the visibly complex, and broad spectrum of disorders that constitute dementia requires the use of a biomechanistic model that is both accurate and general enough to define clinically relevant biomarkers allied to the multiscale cerebral environment. A precision medicine workflow is presented here, which allows for a previously unexplored understanding of the disease trajectory (from mild cognitive impairment [MCI] to AD) through the lens of the physiologically accurate definition and interplay of both the NVU and the glymphatic pathway (by treating this pathway as a separate compartment within a multiporoelastic system).…”

Section: The Vascular Hypothesis Of Ad and The Role Of Hypoperfusionmentioning

confidence: 99%

“… 37 – 39 As described by Benveniste et al, the glymphatic system may be viewed as a waste processing unit, 34 , 40 with the key constituents being: perivascular AQP4 water channels, hydraulic forces associated with arterial pulsation, respiratory effort, and body position, 34 , 41 – 43 regular CSF production and transport, and a state of arousal. 44 , 45 …”

Section: Introductionmentioning

confidence: 99%

Exploring neurodegenerative disorders using a novel integrated model of cerebral transport: Initial results

Vardakis

Chou

Guo

et al. 2020

Proc Inst Mech Eng H

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The neurovascular unit (NVU) underlines the complex and symbiotic relationship between brain cells and the cerebral vasculature, and dictates the need to consider both neurodegenerative and cerebrovascular diseases under the same mechanistic umbrella. Importantly, unlike peripheral organs, the brain was thought not to contain a dedicated lymphatics system. The glymphatic system concept (a portmanteau of glia and lymphatic) has further emphasized the importance of cerebrospinal fluid transport and emphasized its role as a mechanism for waste removal from the central nervous system. In this work, we outline a novel multiporoelastic solver which is embedded within a high precision, subject specific workflow that allows for the co-existence of a multitude of interconnected compartments with varying properties (multiple-network poroelastic theory, or MPET), that allow for the physiologically accurate representation of perfused brain tissue. This novel numerical template is based on a six-compartment MPET system (6-MPET) and is implemented through an in-house finite element code. The latter utilises the specificity of a high throughput imaging pipeline (which has been extended to incorporate the regional variation of mechanical properties) and blood flow variability model developed as part of the VPH-DARE@IT research platform. To exemplify the capability of this large-scale consolidated pipeline, a cognitively healthy subject is used to acquire novel, biomechanistically inspired biomarkers relating to primary and derivative variables of the 6-MPET system. These biomarkers are shown to capture the sophisticated nature of the NVU and the glymphatic system, paving the way for a potential route in deconvoluting the complexity associated with the likely interdependence of neurodegenerative and cerebrovascular diseases. The present study is the first, to the best of our knowledge, that casts and implements the 6-MPET equations in a 3D anatomically accurate brain geometry.

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Cleaning the sleeping brain – the potential restorative function of the glymphatic system

Cited by 83 publications

References 49 publications

Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS

Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS

The Need for Head Space: Brachycephaly and Cerebrospinal Fluid Disorders

Exploring neurodegenerative disorders using a novel integrated model of cerebral transport: Initial results

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