In Vivo Evidence for Impaired Glymphatic Function in the Visual Pathway of Patients With Normal Pressure Hydrocephalus

Jacobsen, Helle J.; Sandell, Tiril; Jørstad, Øystein Kalsnes; Moe, Morten C.; Ringstad, Geir; Eide, Per Kristian

doi:10.1167/iovs.61.13.24

Cited by 20 publications

(23 citation statements)

References 51 publications

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“… Yokota et al (2019) performed diffusion tensor imaging (DTI) along the perivascular space (ALPS) and observed lower diffusivity ALPS in patients with iNPH than in the control group. Other groups reported delayed enrichment and clearance of tracers in the visual pathway of patients with iNPH ( Jacobsen et al, 2020 ).…”

Section: Central Nervous System Diseasesmentioning

confidence: 91%

Glymphatic System Dysfunction in Central Nervous System Diseases and Mood Disorders

Zhang

2022

Front. Aging Neurosci.

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The glymphatic system, a recently discovered macroscopic waste removal system in the brain, has many unknown aspects, especially its driving forces and relationship with sleep, and thus further explorations of the relationship between the glymphatic system and a variety of possible related diseases are urgently needed. Here, we focus on the progress in current research on the role of the glymphatic system in several common central nervous system diseases and mood disorders, discuss the structural and functional abnormalities of the glymphatic system which may occur before or during the pathophysiological progress and the possible underlying mechanisms. We emphasize the relationship between sleep and the glymphatic system under pathological conditions and summarize the common imaging techniques for the glymphatic system currently available. The perfection of the glymphatic system hypothesis and the exploration of the effects of aging and endocrine factors on the central and peripheral regulatory pathways through the glymphatic system still require exploration in the future.

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Section: Central Nervous System Diseasesmentioning

confidence: 91%

Glymphatic System Dysfunction in Central Nervous System Diseases and Mood Disorders

Zhang

2022

Front. Aging Neurosci.

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“…Therefore, these results may support the glymphatic hypothesis in a human population. This demonstration of the glymphatic flow on both contrast-enhanced and non-contrast MRI can have significant clinical value, as such imaging can detect of the glymphatic dysfunction, and can disclose the underlying pathophysiology of certain neurodegenerative diseases, including Alzheimer's disease and normal pressure hydrocephalus ( 53 – 55 ). Therefore, we believe that this systematic review could provide a basis for the future studies linking glymphatic dysfunction and neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

MRI-Based Demonstration of the Normal Glymphatic System in a Human Population: A Systematic Review

et al. 2022

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BackgroundThe glymphatic system has been described as one that facilitates the exchange between the cerebrospinal fluid (CSF) and interstitial fluid, and many recent studies have demonstrated glymphatic flow based on magnetic resonance imaging (MRI). We aim to systematically review the studies demonstrating a normal glymphatic flow in a human population using MRI and to propose a detailed glymphatic imaging protocol.MethodsWe searched the MEDLINE and EMBASE databases to identify studies with human participants involving MRI-based demonstrations of the normal glymphatic flow. We extracted data on the imaging sequence, imaging protocol, and the targeted anatomical structures on each study.ResultsAccording to contrast-enhanced MRI studies, peak enhancement was sequentially detected first in the CSF space, followed by the brain parenchyma, the meningeal lymphatic vessel (MLV), and, finally, the cervical lymph nodes, corresponding with glymphatic flow and explaining the drainage into the MLV. Non-contrast flow-sensitive MRI studies revealed similar glymphatic inflow from the CSF space to the brain parenchyma and efflux of exchanged fluid from the brain parenchyma to the MLV.ConclusionWe may recommend T1-weighted contrast-enhanced MRI for visualizing glymphatic flow. Our result can increase understanding of the glymphatic system and may lay the groundwork for establishing central nervous system fluid dynamic theories and developing standardized imaging protocols.

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“…Another MRI study using intrathecal gadobutrol in human patients with idiopathic normal pressure hydrocephalus showed delayed enhancement and clearance of the tracer in the human visual pathway suggesting an impaired glymphatic pathway in the disease. The tracer distribution within the visual pathway depended on the availability of tracer in the CSF and seemed to be affected by the intracranial compliance 31 .…”

Section: Discussionmentioning

confidence: 99%

A novel maxillofacial technique to deliver drugs to the visual pathway, the optic nerve and the retina using the glymphatic system

Rajendran

Chidambaram

Srikanth

et al. 2022

Preprint

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The blood neural barriers are formidable barriers that prevent delivery of drugs into the eye and the brain. Currently, large biologics are used for treating many diseases of the eye and the brain. But the blood retinal barrier and the blood brain barrier prevent entry of these useful drugs into the eye and the brain respectively. Hence, there is a need for a drug delivery technique to bypass these natural barriers. Bevacizumab (Avastin) is a full length humanized monoclonal antibody with a molecular weight of 149kda. It binds to circulating vascular endothelial growth factor A and prevents interaction with vascular endothelial growth receptors. This results in blocking endothelial response and tumor vascularization. Bevacizumab is used to prevent choroidal neovascularization in age related macular degeneration and to prevent retinal neovascularization in diabetic retinopathy. It is also used for treating certain types of brain cancer. But it crosses neither the blood retinal barrier nor the blood brain barrier. This in vivo mouse study assessed the delivery of a commercial formulation of bevacizumab into the retina of mice using different ocular techniques like topical drops, subconjunctival injection, intravitreal injection and a novel maxillofacial technique. The objective was to assess whether the novel maxillofacial drug delivery technique could deliver drugs into the retina and to compare the efficacy of the maxillofacial technique with the mentioned ocular techniques. The distribution of bevacizumab was further compared with retinoschisin which is a small protein with a molecular weight of 24kda. Intravitreal injection and maxillofacial technique were effective in delivering drugs into the retina. In addition, the maxillofacial technique could target the brain including regions involved in the visual pathway and the optic nerve. The glymphatic pathway could also be targeted for drug delivery. Drug was also detected in the contralateral optic nerve and retina. Based on our study findings, we propose a new concept to explain the presence of the drug in the contralateral eye. We propose that after maxillofacial drug delivery, early distribution of the drug can occur in the CSF at the optic chiasma from the brain via the glymphatic system. In the case of the intravitreal injection, the drug from the experimental eye may be cleared through the glymphatic pathway of the ipsilateral optic nerve into the CSF surrounding the nerve. The crossover of the ipsilateral optic nerve fibers at the optic chiasma can result in further distribution of the drug in the CSF at the optic chiasma. From the region of the optic chiasma, the drug can distribute into the CSF surrounding the contralateral optic nerve. The drug can be then distributed into the contralateral optic nerve through the glymphatic pathway and be delivered into the contralateral eye. The drug can be further cleared into the aqueous of the contralateral eye through the anterior clearance pathway.

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In Vivo Evidence for Impaired Glymphatic Function in the Visual Pathway of Patients With Normal Pressure Hydrocephalus

Cited by 20 publications

References 51 publications

Glymphatic System Dysfunction in Central Nervous System Diseases and Mood Disorders

Glymphatic System Dysfunction in Central Nervous System Diseases and Mood Disorders

MRI-Based Demonstration of the Normal Glymphatic System in a Human Population: A Systematic Review

A novel maxillofacial technique to deliver drugs to the visual pathway, the optic nerve and the retina using the glymphatic system

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