Evidence map›Paper›PMID 33633540›Full record

ReviewFrontiers in neuroscience2021

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

Gianfranco Natale, Fiona Limanaqi, Carla L Busceti, Federica Mastroiacovo, Ferdinando Nicoletti, Stefano Puglisi-Allegra, Francesco Fornai

Open access · goldAbstract readReview
In one paragraph

Review in Frontiers in neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
7.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.

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  4. Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026
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3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Gianfranco NataleDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Fiona LimanaqiDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Carla L BuscetiIRCCS Neuromed, Pozzilli, Italy.
Federica MastroiacovoIRCCS Neuromed, Pozzilli, Italy.
Ferdinando NicolettiIRCCS Neuromed, Pozzilli, Italy.
Stefano Puglisi-AllegraIRCCS Neuromed, Pozzilli, Italy.
Francesco FornaiDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Istituto Neurologico Mediterraneo · ITUniversity of Pisa · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

blood–brain barrierglymphatic systemlymphatic systemneurodegenerative diseasesneurovascular unit

Identifiers

PMID33633540
PMCPMC7900543
OpenAlexW3127628642

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.