Paravascular spaces at the brain surface: Low resistance pathways for cerebrospinal fluid flow

Bedussi, Beatrice; Almasian, Mitra; Vos, Judith de; VanBavel, Ed; Bakker, Erik N. T. P.

doi:10.1177/0271678x17737984

Cited by 158 publications

(317 citation statements)

References 23 publications

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“…First reported by Iliff et al, the glymphatic pathway involves the “paravascular space,” which drains interstitial fluid and cerebrospinal fluid (CSF) from the para‐arterial space via glial parenchyma to the para‐venous space, finally into the internal cerebral vein. As a low‐resistant drainage pathway, pulsatile paravascular flow generated by the cardiac cycle was observed . Of note, the so‐called “paravascular space” referred to by Iliff is located between the glial limitans and the vascular BM, which is actually VRS where PVMs reside.…”

Section: Pvm Functions In the Normal Brainmentioning

confidence: 99%

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Brain perivascular macrophages: Recent advances and implications in health and diseases

2019

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Brain perivascular macrophages (PVMs) belong to a distinct population of brain‐resident myeloid cells located within the perivascular space surrounding arterioles and venules. Their characterization depends on the combination of anatomical localization, phagocytic capacity, and molecular markers. Under physiological status, they provide structural and functional support for maintaining brain homeostasis, including facilitation of blood‐brain barrier integrity and lymphatic drainage, and exertion of immune functions such as phagocytosis and antigen presentation. Increasing evidence also implicates their specific roles in diseased brain, ranging from cerebrovascular diseases, Aβ pathologies, infections, and autoimmunity. Collectively, PVMs are key components of the brain‐resident immune system, actively participate in a broad‐spectrum of processes in normal and diseased status. Details of the processes are largely underexplored. Targeting PVMs would lead to new insights and be a promising strategy for a broad array of human diseases.

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Section: Pvm Functions In the Normal Brainmentioning

confidence: 99%

“…As a lowresistant drainage pathway, pulsatile paravascular flow generated by the cardiac cycle was observed. 48 Of note, the so-called "paravascular space" referred to by Iliff is located between the glial limitans and the vascular BM, which is actually VRS where PVMs reside.…”

Section: Lymphatic Clearancementioning

confidence: 99%

Brain perivascular macrophages: Recent advances and implications in health and diseases

2019

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“…This was based on analysis of in vivo tracer spreading, using two-photon imaging, and ex vivo fluorescence microscopy on brain slices. Using microsphere tracking, recent work from our group confirmed that at the brain surface, CSF flows along arteries in the direction of blood flow in a pulsatile manner (Bedussi, Almasian, de Vos, VanBavel, & Bakker, 2018). Further confirmation of this flow pattern in a noninvasive manner was provided by the work of Harrison et al (2018).…”

Section: The Paravascular Space and Direction Of Flowmentioning

confidence: 76%

“…Our data show that the paravascular spaces at the level of the meninges is continuous with the subarachnoid space (SAS) and appears as a widening created by meningeal blood vessels. This widening of the SAS is particularly large around arteries, probably because of the rounded shape in comparison to the more flattened veins, and can be observed in both humans and rodents (Bedussi et al, 2018). Weller and Carare refer to perivascular flow along basement membranes that starts at the level of the capillaries and travels upstream along arterial smooth muscle cells.…”

Section: • What Advances Does It Highlight?mentioning

confidence: 99%

Paravascular spaces: entry to or exit from the brain?

Bakker

Naessens

VanBavel

2019

Experimental Physiology

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New Findings What is the topic of this review? In this symposium report, we review the glymphatic clearance from the brain. What advances does it highlight? Evaluation of the evidence indicates that cerebrospinal fluid flows along paravascular spaces at the surface of the brain. However, bulk flow along penetrating arteries into the brain, followed by exit along veins, requires further confirmation. Clearance from the brain, based on mixing, might provide an alternative explanation for experimental findings. Abstract The interstitial fluid of the brain provides the environment for proper neuronal function. Maintenance of the volume and composition of interstitial fluid requires regulation of the influx and removal of water, ions, nutritive and waste products. The recently described glymphatic pathway might contribute to some of these functions. It is proposed that cerebrospinal fluid enters the brain via paravascular spaces along arteries, mixes with interstitial fluid, and leaves the brain via paravascular spaces along veins. In this symposium report, we review the glymphatic concept, its concerns, and alternative views on interstitial fluid–cerebrospinal fluid exchange.

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“…The main bulk of evidence for the glymphatic pathway has been established via in-vivo rodent experiments. In these experiments, tracers are typically infused in the CSF in rodents at a rate of 0.34-2 µL/min, with a resulting pressure increase of 0.1-2.5 mmHg [31,5,46]. Thus, such tracer experiments may in fact be viewed as infusion tests.…”

Section: Introductionmentioning

confidence: 99%

Intracranial pressure elevation alters CSF clearance pathways

Vinje

Eklund

Mardal

et al. 2019

Preprint

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AbstractBackgroundInfusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding mathematical models that describe the CSF circulation from the choroid plexus to the arachnoid granulations. Here, we investigate to what extent the proposed glymphatic or paravascular pathway (or similar pathways) modifies the results of the traditional mathematical models.MethodsWe used a two-compartment model consisting of the subarachnoid space and the paravascular spaces. For the arachnoid granulations, the cribriform plate, capillaries and paravascular spaces, resistances were calculated and used to estimate flow before and during an infusion test. Next, pressure in the subarachnoid space and paravascular spaces were computed. Finally, different variations to the model were tested to evaluate the sensitivity of selected parameters.ResultsAt baseline, we found a very small paravascular flow directed into the subarachnoid space, while 60% of the fluid left through the arachnoid granulations and 40% left through the cribriform plate. However, during the infusion, paravascular flow reversed and 25% of the fluid left through these spaces, while 60% went through the arachnoid granulations and only 15% through the cribriform plate.ConclusionsThe relative distribution of CSF flow to different clearance pathways depends on intracranial pressure (ICP), with the arachnoid granulations as the main contributor to outflow. As such, ICP increase is an important factor that should be addressed when determining the pathways of injected substances in the subarachnoid space.

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Paravascular spaces at the brain surface: Low resistance pathways for cerebrospinal fluid flow

Cited by 158 publications

References 23 publications

Brain perivascular macrophages: Recent advances and implications in health and diseases

Brain perivascular macrophages: Recent advances and implications in health and diseases

Paravascular spaces: entry to or exit from the brain?

Intracranial pressure elevation alters CSF clearance pathways

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