Magnetic Resonance Imaging and Modeling of the Glymphatic System

Kaur, J.; Davoodi‐Bojd, Esmaeil; Fahmy, Lara M.; Zhang, Li; Ding, Guangliang; Hu, Jiani; Zhang, Zhenggang; Chopp, Michael; Jiang, Quan

doi:10.3390/diagnostics10060344

Cited by 25 publications

(22 citation statements)

References 132 publications

(227 reference statements)

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“…The glymphatic pathway is being widely investigated comparing healthy and pathological conditions, such as neurodegenerative disorders, including chronic Alzheimer’s disease (AD), as well as hemorrhagic and ischemic stroke, hydrocephalus or traumatic brain injury. Descriptions in human disorders were backed up by experimental modeling of the system, which was developed to predict a potential site of therapeutic intervention ( Rasmussen et al, 2018 ; Jiang, 2019 ; Ramos et al, 2019 ; Kaur et al, 2020 ; Reeves et al, 2020 ). Novel anatomical insights were provided indicating that the midbrain, due to the consistent thickness of its pial-glial BM, is better equipped for convective influx/glymphatic entry of the CSF compared with other brain regions.…”

Section: Introduction: Classic Anatomical Conceptsmentioning

confidence: 99%

“…Many controversies and open issues exist concerning the perivascular and paravascular models, including the opposite directions of fluid flow, anatomical and functional differences, potential driving forces, and their role in health and disease ( Bakker et al, 2016 ; Bacyinski et al, 2017 ). Some morphological and functional studies postulated an alternative hypothesis, which considers diffusion (not convective bulk flow) as the main mechanism regulating CSF-ISF exchange at the level of the NVU associated with brain capillaries, and throughout the interstitial space ( Asgari et al, 2016 ; Jin et al, 2016 ; Smith et al, 2017 ; Abbott et al, 2018 ; Bakker et al, 2019 ; Kaur et al, 2020 ).…”

Section: Introduction: Classic Anatomical Conceptsmentioning

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: Introduction: Classic Anatomical Conceptsmentioning

confidence: 99%

Section: Introduction: Classic Anatomical Conceptsmentioning

confidence: 99%

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

et al. 2021

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“…To date, the most successful method to measure the glymphatic system in patients is with MRI [28,53,[70][71][72]. We previously reviewed the use of serial MRI after intrathecal Gad (also called dynamic contrast-enhanced MRI) to study the glymphatic system in near-normal control subjects and patients with NPH [28,53].…”

Section: Current and Emerging Methods To Measure Glymphatic Functionmentioning

confidence: 99%

Does Impaired Glymphatic Drainage Cause Glymphedema? A Review Tailored to Neurocritical Care and Neurosurgery

Akins¹,

Guppy²

2021

Neurocrit Care

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Research into the glymphatic system reached an inflection point with steep trajectory in 2012 when it was formally recognized and named, but the historical roots for it are solid and deep, dating back to pioneers such as Cushing, Weed, and Dandy. We provide an overview of key discoveries of the glymphatic system, which promotes bulk flow of fluid and solutes throughout the brain parenchyma. We also discuss the lymphatic drainage of the central nervous system. Evidence is building that failure of the glymphatic system causes glymphedema in patients commonly managed by neurocritical care and neurosurgery specialists. We review research supporting this for decompressive craniectomy, subarachnoid hemorrhage, and normal-pressure hydrocephalus. We argue that it is time for a paradigm shift from the traditional model of cerebrospinal fluid circulation to a revised model that incorporates the glymphatic pathway and lymphatic clearance. These recent breakthroughs will inspire new therapeutic approaches to recognize, reverse, and restore glymphatic dysfunction and to leverage this pathway to deliver brain-wide therapeutics.

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“…The bulk of the glymphatic systems is attributed to the functions of astrocytes; the aforementioned astrocytic water channel AQP-4 is the crucial mediator of the exchange of ISF and CSF, which overall acts much in the manner of a pseudolymphatic system, governed by circadian rhythm in the CNS [ 54 , 73 , 74 ]. Interestingly, AQP-4 channels not only play a critical role in the homeostasis in the CNS, but they also have a clinically significant supportive role in other sensory and metabolic organs [ 49 , 54 , 73 , 74 ]. The mean rate of CSF production is 0.4 mL per minute in healthy humans and 0.2 mL per minute in patients with AD [ 75 ].…”

Section: Main Textmentioning

confidence: 99%

“…In a review article, Mader and Brimberg (2019) laid out that AQP-4 may be a factor in a number of pathologies [ 73 ]. Some of the neurodegenerative diseases such as AxD, AD, ALS, PD, as well as stroke, trauma, and psychiatric diseases (e.g., schizophrenia, major depressive disorder, and ASD) are accompanied by dysfunctional AQP-4 and, thereby, the glymphatic system.…”

Section: Main Textmentioning

confidence: 99%

A Destruction Model of the Vascular and Lymphatic Systems in the Emergence of Psychiatric Symptoms

Segawa

Blumenthal

Yamawaki

et al. 2021

Biology

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The lymphatic system is important for antigen presentation and immune surveillance. The lymphatic system in the brain was originally introduced by Giovanni Mascagni in 1787, while the rediscovery of it by Jonathan Kipnis and Kari Kustaa Alitalo now opens the door for a new interpretation of neurological diseases and therapeutic applications. The glymphatic system for the exchanges of cerebrospinal fluid (CSF) and interstitial fluid (ISF) is associated with the blood-brain barrier (BBB), which is involved in the maintenance of immune privilege and homeostasis in the brain. Recent notions from studies of postmortem brains and clinical studies of neurodegenerative diseases, infection, and cerebral hemorrhage, implied that the breakdown of those barrier systems and infiltration of activated immune cells disrupt the function of both neurons and glia in the parenchyma (e.g., modulation of neurophysiological properties and maturation of myelination), which causes the abnormality in the functional connectivity of the entire brain network. Due to the vulnerability, such dysfunction may occur in developing brains as well as in senile or neurodegenerative diseases and may raise the risk of emergence of psychosis symptoms. Here, we introduce this hypothesis with a series of studies and cellular mechanisms.

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Magnetic Resonance Imaging and Modeling of the Glymphatic System

Cited by 25 publications

References 132 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

Does Impaired Glymphatic Drainage Cause Glymphedema? A Review Tailored to Neurocritical Care and Neurosurgery

A Destruction Model of the Vascular and Lymphatic Systems in the Emergence of Psychiatric Symptoms

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