The glymphatic system: Current understanding and modeling

Bohr, Tomas; Hjorth, Poul G.; Holst, Sebastian C.; Hrabětová, Sabina; Kiviniemi, Vesa; Lilius, Tuomas; Lundgaard, Iben; Mardal, Kent‐André; Martens, Erik Andreas; Mori, Yutaka; Nägerl, U. Valentin; Nicholson, Charles; Tannenbaum, Allen; Thomas, John H.; Tithof, Jeffrey; Benveniste, Helene; Iliff, Jeffrey J.; Kelley, Douglas H.; Nedergaard, Maiken

doi:10.1016/j.isci.2022.104987

Cited by 104 publications

(91 citation statements)

References 268 publications

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“…A basic concept of the CSF circulatory system is that CSF channels travel in close proximity to the vascular system. This is true in the sagittal sinus (adjacent to superior sagittal sinus vein); in the neck (within adventitia of internal jugular vein); and even with the intra-cranial paravascular glymphatic vessels described by Iliff and others (16)(17)(18).…”

Section: Discussionmentioning

confidence: 88%

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Identification of a novel path for cerebrospinal fluid (CSF) drainage of the human brain

Pessa¹

2023

Preprint

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A novel extravenous pathway is described that drains cerebrospinal fluid from the subarachnoid space to the thoracic duct. Cadaver dissection identifies the cerebrospinal fluid canalicular system as a series of channels that travel within the dural superior sagittal sinus. The anatomic pathway is described in detail. The possible relationship to spaceflight associated neuro ocular syndrome is discussed.

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Section: Discussionmentioning

confidence: 88%

“…The copyright holder for this preprint this version posted January 14, 2023. ; https://doi.org/10.1101/2023.01.13.23284147 doi: medRxiv preprint the intra-cranial paravascular glymphatic vessels described by Iliff and others (16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel path for cerebrospinal fluid (CSF) drainage of the human brain

Pessa¹

2023

Preprint

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“…The localization of AQP4 on the endfeet of astrocytes is responsible for the flow of water from the blood vessels into the brain parenchyma. This flow is called the glymphatic system [ 28 ]. The glymphatic system has been suggested to be responsible for clearing waste products and pathogenic substances from the brain parenchyma, and it also contributes to the clearance of amyloid β40 [ 29 ], suggesting that the disruption of BBB integrity contributes to the onset of Alzheimer’s disease (AD).…”

Section: Astrocytes and The Extracellular Matrixmentioning

confidence: 99%

Astrocytic Neuroimmunological Roles Interacting with Microglial Cells in Neurodegenerative Diseases

Gotoh

Miyamoto

Ikeshima-Kataoka

2023

IJMS

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Both astrocytic and microglial functions have been extensively investigated in healthy subjects and neurodegenerative diseases. For astrocytes, not only various sub-types were identified but phagocytic activity was also clarified recently and is making dramatic progress. In this review paper, we mostly focus on the functional role of astrocytes in the extracellular matrix and on interactions between reactive astrocytes and reactive microglia in normal states and in neurodegenerative diseases, because the authors feel it is necessary to elucidate the mechanisms among activated glial cells in the pathology of neurological diseases in order to pave the way for drug discovery. Finally, we will review cyclic phosphatidic acid (cPA), a naturally occurring phospholipid mediator that induces a variety of biological activities in the brain both in vivo and in vitro. We propose that cPA may serve as a novel therapeutic molecule for the treatment of brain injury and neuroinflammation.

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“…Multiple models have been proposed to explain the fluid flow that occurs in and around perivascular spaces ( Hladky and Barrand, 2014 , 2022 ; Bohr et al, 2022 ). According to one widely held model, CSF flushes out from the periarteriolar spaces, via mechanisms including convective fluid flow and arterial pulsations, into the interstitial space to flush waste metabolites towards perivenular spaces ( Figure 1 ; Troili et al, 2020 ).…”

Section: The Glymphatic System and Perivascular Spacesmentioning

confidence: 99%

A critical guide to the automated quantification of perivascular spaces in magnetic resonance imaging

Pham

Lynch²,

Spitz³

et al. 2022

Front. Neurosci.

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The glymphatic system is responsible for waste clearance in the brain. It is comprised of perivascular spaces (PVS) that surround penetrating blood vessels. These spaces are filled with cerebrospinal fluid and interstitial fluid, and can be seen with magnetic resonance imaging. Various algorithms have been developed to automatically label these spaces in MRI. This has enabled volumetric and morphological analyses of PVS in healthy and disease cohorts. However, there remain inconsistencies between PVS measures reported by different methods of automated segmentation. The present review emphasizes that importance of voxel-wise evaluation of model performance, mainly with the Sørensen Dice similarity coefficient. Conventional count correlations for model validation are inadequate if the goal is to assess volumetric or morphological measures of PVS. The downside of voxel-wise evaluation is that it requires manual segmentations that require large amounts of time to produce. One possible solution is to derive these semi-automatically. Additionally, recommendations are made to facilitate rigorous development and validation of automated PVS segmentation models. In the application of automated PVS segmentation tools, publication of image quality metrics, such as the contrast-to-noise ratio, alongside descriptive statistics of PVS volumes and counts will facilitate comparability between studies. Lastly, a head-to-head comparison between two algorithms, applied to two cohorts of astronauts reveals how results can differ substantially between techniques.

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The glymphatic system: Current understanding and modeling

Cited by 104 publications

References 268 publications

Identification of a novel path for cerebrospinal fluid (CSF) drainage of the human brain

Identification of a novel path for cerebrospinal fluid (CSF) drainage of the human brain

Astrocytic Neuroimmunological Roles Interacting with Microglial Cells in Neurodegenerative Diseases

A critical guide to the automated quantification of perivascular spaces in magnetic resonance imaging

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