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Glymphatics

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https://www.readbyqxmd.com/read/29344300/general-anesthesia-inhibits-the-activity-of-the-glymphatic-system
#1
Clement Gakuba, Thomas Gaberel, Suzanne Goursaud, Jennifer Bourges, Camille Di Palma, Aurélien Quenault, Sara Martinez de Lizarrondo, Denis Vivien, Maxime Gauberti
INTRODUCTION: According to the "glymphatic system" hypothesis, brain waste clearance is mediated by a continuous replacement of the interstitial milieu by a bulk flow of cerebrospinal fluid (CSF). Previous reports suggested that this cerebral CSF circulation is only active during general anesthesia or sleep, an effect mediated by the dilatation of the extracellular space. Given the controversies regarding the plausibility of this phenomenon and the limitations of currently available methods to image the glymphatic system, we developed original whole-brain in vivo imaging methods to investigate the effects of general anesthesia on the brain CSF circulation...
2018: Theranostics
https://www.readbyqxmd.com/read/29279202/the-emerging-relationship-between-interstitial-fluid-cerebrospinal-fluid-exchange-amyloid-%C3%AE-and-sleep
#2
REVIEW
Erin L Boespflug, Jeffrey J Iliff
Amyloid-β (Aβ) plaques are a key histopathological hallmark of Alzheimer's disease (AD), and soluble Aβ species are believed to play an important role in the clinical development of this disease. Emerging biomarker data demonstrate that Aβ plaque deposition begins decades before the onset of clinical symptoms, suggesting that understanding the biological determinants of the earliest steps in the development of AD pathology may provide key opportunities for AD treatment and prevention. Although a clinical association between sleep disruption and AD has long been appreciated, emerging clinical studies and insights from the basic neurosciences have shed important new light on how sleep and Aβ homeostasis may be connected in the setting of AD...
February 15, 2018: Biological Psychiatry
https://www.readbyqxmd.com/read/29195051/the-glymphatic-system-in-central-nervous-system-health-and-disease-past-present-and-future
#3
Benjamin A Plog, Maiken Nedergaard
The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudolymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters the brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute...
December 1, 2017: Annual Review of Pathology
https://www.readbyqxmd.com/read/29163074/the-paravascular-pathway-for-brain-waste-clearance-current-understanding-significance-and-controversy
#4
REVIEW
Andrew Bacyinski, Maosheng Xu, Wei Wang, Jiani Hu
The paravascular pathway, also known as the "glymphatic" pathway, is a recently described system for waste clearance in the brain. According to this model, cerebrospinal fluid (CSF) enters the paravascular spaces surrounding penetrating arteries of the brain, mixes with interstitial fluid (ISF) and solutes in the parenchyma, and exits along paravascular spaces of draining veins. Studies have shown that metabolic waste products and solutes, including proteins involved in the pathogenesis of neurodegenerative diseases such as amyloid-beta, may be cleared by this pathway...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/29121965/chronic-cerebral-hypoperfusion-induces-post-stroke-dementia-following-acute-ischemic-stroke-in-rats
#5
Dong Bin Back, Kyoung Ja Kwon, Dong-Hee Choi, Chan Young Shin, Jongmin Lee, Seol-Heui Han, Hahn Young Kim
BACKGROUND: Post-stroke dementia (PSD) is one of the major consequences after stroke. Chronic cerebral hypoperfusion (CCH) can induce vascular cognitive impairment and potentiate amyloid pathology. We investigated how CCH contributes to the development of PSD after stroke in the context of neuroinflammation and amyloid pathology. METHODS: We designed a unique animal model for PSD. We performed middle cerebral artery occlusion (MCAO) surgery in rats mimicking acute territorial infarct, which was followed by bilateral common carotid artery occlusion (BCCAo) surgery mimicking CCH...
November 9, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29101220/the-glymphatic-mechanism-for-solute-clearance-in-alzheimer-s-disease-game-changer-or-unproven-speculation
#6
REVIEW
Alex J Smith, Alan S Verkman
How solutes and macromolecules are removed from brain tissue is of central importance in normal brain physiology and in how toxic protein aggregates are cleared in neurodegenerative conditions, including Alzheimer's disease (AD). Conventionally, solute transport in the narrow and tortuous extracellular space in brain parenchyma has been thought to be primarily diffusive and nondirectional. The recently proposed "glymphatic" (glial-lymphatic) hypothesis posits that solute clearance is convective and driven by active fluid transport from para-arterial to paravenous spaces though aquaporin-4 water channels in astrocyte endfeet...
November 3, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29079431/voluntary-running-enhances-glymphatic-influx-in-awake-behaving-young-mice
#7
Stephanie von Holstein-Rathlou, Nicolas Caesar Petersen, Maiken Nedergaard
Vascular pathology and protein accumulation contribute to cognitive decline, whereas exercise can slow vascular degeneration and improve cognitive function. Recent investigations suggest that glymphatic clearance measured in aged mice while anesthetized is enhanced following exercise. We predicted that exercise would also stimulate glymphatic activity in awake, young mice with higher baseline glymphatic function. Therefore, we assessed glymphatic function in young female C57BL/6J mice following five weeks voluntary wheel running and in sedentary mice...
January 1, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29067342/the-effects-of-noncoding-aquaporin-4-single-nucleotide-polymorphisms-on-cognition-and-functional-progression-of-alzheimer-s-disease
#8
Kevin G Burfeind, Charles F Murchison, Shawn K Westaway, Matthew J Simon, Deniz Erten-Lyons, Jeffrey A Kaye, Joseph F Quinn, Jeffrey J Iliff
INTRODUCTION: The glymphatic system is a brain-wide perivascular network that facilitates clearance of proteins, including amyloid β, from the brain interstitium through the perivascular exchange of cerebrospinal fluid and interstitial fluid. The astrocytic water channel aquaporin-4 (AQP4) is required for glymphatic system function, and impairment of glymphatic function in the aging brain is associated with altered AQP4 expression and localization. In human cortical tissue, alterations in AQP4 expression and localization are associated with Alzheimer's disease (AD) status and pathology...
September 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/29024871/brain-energetics-during-the-sleep-wake-cycle
#9
REVIEW
Mauro DiNuzzo, Maiken Nedergaard
Brain activity during wakefulness is associated with high metabolic rates that are believed to support information processing and memory encoding. In spite of loss of consciousness, sleep still carries a substantial energy cost. Experimental evidence supports a cerebral metabolic shift taking place during sleep that suppresses aerobic glycolysis, a hallmark of environment-oriented waking behavior and synaptic plasticity. Recent studies reveal that glial astrocytes respond to the reduction of wake-promoting neuromodulators by regulating volume, composition and glymphatic drainage of interstitial fluid...
October 9, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29021222/the-perivascular-pathways-for-influx-of-cerebrospinal-fluid-are-most-efficient-in-the-midbrain
#10
Howard Dobson, Matthew MacGregor Sharp, Richard Cumpsty, Theodore P Criswell, Tyler Wellman, Ciara Finucane, Jenna M Sullivan, Roy O Weller, Ajay Verma, Roxana O Carare
Although there are no conventional lymphatic vessels in the brain, fluid and solutes drain along basement membranes of cerebral capillaries and arteries towards the subarachnoid space and cervical lymph nodes. Convective influx/glymphatic entry of the cerebrospinal fluid (CSF) into the brain parenchyma occurs along the pial-glial basement membranes of arteries. This project tested the hypotheses that pial-glial basement membranes of arteries are thicker in the midbrain, allowing more glymphatic entry of CSF...
October 11, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28991102/why-a-one-way-ticket-to-mars-may-result-in-one-way-directional-glymphatic-flow-to-the-eye-response
#11
Thomas H Mader, C Robert Gibson, Christian A Otto, Ashot E Sargsyan, Neil R Miller, Prem S Subramanian, Stephen F Hart, William Lipsky, Nimesh B Patel, Andrew G Lee
No abstract text is available yet for this article.
December 2017: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
https://www.readbyqxmd.com/read/28991101/why-a-one-way-ticket-to-mars-may-result-in-a-one-way-directional-glymphatic-flow-to-the-eye
#12
Peter Wostyn, Hanspeter Esriel Killer, Peter Paul De Deyn
No abstract text is available yet for this article.
December 2017: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
https://www.readbyqxmd.com/read/28973323/evidence-for-cerebrospinal-fluid-entry-into-the-optic-nerve-via-a-glymphatic-pathway
#13
Emily Mathieu, Neeru Gupta, Amir Ahari, Xun Zhou, Joseph Hanna, Yeni H Yücel
Purpose: The purpose of this study was to determine whether cerebrospinal fluid (CSF) enters the optic nerve via a glymphatic pathway and whether this entry is size-dependent. Methods: Fluorescent dextran tracers (fluorescein isothiocyanate [FITC]) of four different sizes (10, 40, 70, and 500 kDa) and FITC-ovalbumin (45 kDa) were injected into the CSF of 15 adult mice. Tracer distribution in the orbital optic nerve at 1 hour after injection was assessed in tissue sections with confocal microscopy...
September 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28969373/glymphatic-mri-in-idiopathic-normal-pressure-hydrocephalus
#14
Geir Ringstad, Svein Are Sirirud Vatnehol, Per Kristian Eide
The glymphatic system has in previous studies been shown as fundamental to clearance of waste metabolites from the brain interstitial space, and is proposed to be instrumental in normal ageing and brain pathology such as Alzheimer's disease and brain trauma. Assessment of glymphatic function using magnetic resonance imaging with intrathecal contrast agent as a cerebrospinal fluid tracer has so far been limited to rodents. We aimed to image cerebrospinal fluid flow characteristics and glymphatic function in humans, and applied the methodology in a prospective study of 15 idiopathic normal pressure hydrocephalus patients (mean age 71...
October 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28948167/the-glymphatic-hypothesis-of-glaucoma-a-unifying-concept-incorporating-vascular-biomechanical-and-biochemical-aspects-of-the-disease
#15
REVIEW
Peter Wostyn, Veva De Groot, Debby Van Dam, Kurt Audenaert, Hanspeter Esriel Killer, Peter Paul De Deyn
The pathophysiology of primary open-angle glaucoma is still largely unknown, although a joint contribution of vascular, biomechanical, and biochemical factors is widely acknowledged. Since glaucoma is a leading cause of irreversible blindness worldwide, exploring its underlying pathophysiological mechanisms is extremely important and challenging. Evidence from recent studies appears supportive of the hypothesis that a "glymphatic system" exists in the eye and optic nerve, analogous to the described "glymphatic system" in the brain...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28938276/anesthesia-with-dexmedetomidine-and-low-dose-isoflurane-increases-solute-transport-via-the-glymphatic-pathway-in-rat-brain-when-compared-with-high-dose-isoflurane
#16
COMPARATIVE STUDY
Helene Benveniste, Hedok Lee, Fengfei Ding, Qian Sun, Ehab Al-Bizri, Rany Makaryus, Stephen Probst, Maiken Nedergaard, Elliot A Stein, Hanbing Lu
BACKGROUND: The glymphatic pathway transports cerebrospinal fluid through the brain, thereby facilitating waste removal. A unique aspect of this pathway is that its function depends on the state of consciousness of the brain and is associated with norepinephrine activity. A current view is that all anesthetics will increase glymphatic transport by inducing unconsciousness. This view implies that the effect of anesthetics on glymphatic transport should be independent of their mechanism of action, as long as they induce unconsciousness...
December 2017: Anesthesiology
https://www.readbyqxmd.com/read/28903061/lymphatic-drainage-system-of-the-brain-a-novel-target-for-intervention-of-neurological-diseases
#17
REVIEW
Bao-Liang Sun, Li-Hua Wang, Tuo Yang, Jing-Yi Sun, Lei-Lei Mao, Ming-Feng Yang, Hui Yuan, Robert A Colvin, Xiao-Yi Yang
The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes. The brain lymphatic systems function physiological as a route of drainage for interstitial fluid (ISF) from brain parenchyma to nearby lymph nodes...
September 10, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28862640/understanding-the-functions-and-relationships-of-the-glymphatic-system-and-meningeal-lymphatics
#18
REVIEW
Antoine Louveau, Benjamin A Plog, Salli Antila, Kari Alitalo, Maiken Nedergaard, Jonathan Kipnis
Recent discoveries of the glymphatic system and of meningeal lymphatic vessels have generated a lot of excitement, along with some degree of skepticism. Here, we summarize the state of the field and point out the gaps of knowledge that should be filled through further research. We discuss the glymphatic system as a system that allows CNS perfusion by the cerebrospinal fluid (CSF) and interstitial fluid (ISF). We also describe the recently characterized meningeal lymphatic vessels and their role in drainage of the brain ISF, CSF, CNS-derived molecules, and immune cells from the CNS and meninges to the peripheral (CNS-draining) lymph nodes...
September 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28859995/glymphatic-system-disruption-as-a-mediator-of-brain-trauma-and-chronic-traumatic-encephalopathy
#19
REVIEW
Molly J Sullan, Breton M Asken, Michael S Jaffee, Steven T DeKosky, Russell M Bauer
Traumatic brain injury (TBI) is an increasingly important issue among veterans, athletes and the general public. Difficulties with sleep onset and maintenance are among the most commonly reported symptoms following injury, and sleep debt is associated with increased accumulation of beta amyloid (Aβ) and phosphorylated tau (p-tau) in the interstitial space. Recent research into the glymphatic system, a lymphatic-like metabolic clearance mechanism in the central nervous system (CNS) which relies on cerebrospinal fluid (CSF), interstitial fluid (ISF), and astrocytic processes, shows that clearance is potentiated during sleep...
August 30, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28826498/test-of-the-glymphatic-hypothesis-demonstrates-diffusive-and-aquaporin-4-independent-solute-transport-in-rodent-brain-parenchyma
#20
Alex J Smith, Xiaoming Yao, James A Dix, Byung-Ju Jin, Alan S Verkman
Transport of solutes through brain involves diffusion and convection. The importance of convective flow in the subarachnoid and paravascular spaces has long been recognized; a recently proposed 'glymphatic' clearance mechanism additionally suggests that aquaporin-4 (AQP4) water channels facilitate convective transport through brain parenchyma. Here, the major experimental underpinnings of the glymphatic mechanism were re-examined by measurements of solute movement in mouse brain following intracisternal or intraparenchymal solute injection...
August 21, 2017: ELife
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