Evidence map›Paper›PMID 31209176›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2019

Impaired Glymphatic Transport in Spontaneously Hypertensive Rats.

Kristian Nygaard Mortensen, Simon Sanggaard, Humberto Mestre, Hedok Lee, Serhii Kostrikov, Anna L R Xavier, Albert Gjedde, Helene Benveniste, Maiken Nedergaard

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
153citing papers in PubMed, 2 pooled it
10.1field-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

153 citing papers in PubMed, 2 syntheses or guidelines pooled it, 267 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Glymphatic function in humans: indicators, modulators, and measurement strategies.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Review
  6. Article
  7. Review
  8. Review
  9. The glymphatic system and Parkinson's disease: a narrative review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Review
  10. The role of glymphatic dysfunction in cerebral small vessel disease and vascular cognitive impairment, and therapeutic implications.International journal of stroke : official journal of the International Stroke Society · 2026
    Review
  11. Review
  12. Unveiling the glymphatic system's role in brain aging: A comprehensive biomarker and modifiable intervention target.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  13. Quantitative assessment of flow between cerebrospinal and interstitial fluid compartments in humans.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  14. Review
  15. Article
  16. Hypertensive Brain Injury as a Journey Not a Destination.Journal of the American Heart Association · 2026
    Article
  17. Article
  18. Article
  19. Article
  20. Article

93 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

9 authors at 4 institutions in 3 countries.

Kristian Nygaard MortensenCenter for Translational Neuromedicine, University of Copenhagen, Copenhagen N, Denmark, 2200.ORCID 0000-0003-3726-0781
Simon SanggaardCenter for Translational Neuromedicine, University of Copenhagen, Copenhagen N, Denmark, 2200.
Humberto MestreCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642.ORCID 0000-0001-5876-5397
Hedok LeeDepartment of Anesthesiology, Yale School of Medicine, Yale University, New Haven, Connecticut 06520-8051.
Serhii KostrikovCenter for Translational Neuromedicine, University of Copenhagen, Copenhagen N, Denmark, 2200.
Anna L R XavierCenter for Translational Neuromedicine, University of Copenhagen, Copenhagen N, Denmark, 2200.ORCID 0000-0001-5143-6531
Albert GjeddeDepartments of Clinical Research and Nuclear Medicine, Odense University Hospital, University of Southern Denmark, Odense C, Denmark 5000, and.ORCID 0000-0002-3756-7401
Helene BenvenisteDepartment of Anesthesiology, Yale School of Medicine, Yale University, New Haven, Connecticut 06520-8051.ORCID 0000-0002-2887-6667
Maiken NedergaardCenter for Translational Neuromedicine, University of Copenhagen, Copenhagen N, Denmark, 2200, nedergaard@sund.ku.dk.
University of Copenhagen · DKYale University · USMontreal Neurological Institute and Hospital · CAUniversity of Rochester Medical Center · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Para-Vascular Basis of Small Vessel DiseaseR01NS100366 · NINDS · UNIVERSITY OF ROCHESTER · PI NEDERGAARD, MAIKEN · 2016 to 2020
$3.8M
Age and AD related bottlenecks in glymphatic-lymphatic waste transportRF1AG057575 · NIA · UNIVERSITY OF ROCHESTER · PI NEDERGAARD, MAIKEN · 2017 to 2017
$3.2M
Capillary hyperemia in white matter: Novel mechanistic insight and effect of hypertension and agingRF1NS110049 · NINDS · UNIVERSITY OF ROCHESTER · PI NEDERGAARD, MAIKEN, WAN, JIANDI · 2018 to 2018
$2.9M
Glymphatic function in a transgenic rat model of Alzheimer's diseaseR01AG048769 · NIA · UNIVERSITY OF ROCHESTER · PI BENVENISTE, HELENE D, NEDERGAARD, MAIKEN · 2014 to 2018
$1.4M
NCATS NIH HHS UL1 TR001863NIA NIH HHS R01 AG048769NIA NIH HHS RF1 AG057575NINDS NIH HHS R01 NS100366NINDS NIH HHS RF1 NS110049
6 · The paper itself

Abstract

The glymphatic system is a brainwide CSF transport system that uses the perivascular space for fast inflow of CSF. Arterial pulsations are a major driver of glymphatic CSF inflow, and hypertension that causes vascular pathologies, such as arterial stiffening and perivascular alterations, may impede the inflow. We used dynamic contrast-enhanced MRI to assess the effect of hypertension on glymphatic transport kinetics in male young and adult spontaneously hypertensive (SHR) rats compared with age-matched normotensive Wistar-Kyoto rats (WKY). We anesthetized the rats with dexmedetomidine/isoflurane and infused paramagnetic contrast (Gd-DOTA) into the cisterna magna during dynamic contrast-enhanced MRI to quantify glymphatic transport kinetics. Structural MRI analysis showed that cerebroventricular volumes are larger and brain volumes significantly smaller in SHR compared with WKY rats, regardless of age. We observed ventricular reflux of Gd-DOTA in SHR rats only, indicating abnormal CSF flow dynamics secondary to innate hydrocephalus. One-tissue compartment analysis revealed impeded glymphatic transport of Gd-DOTA in SHR compared with WKY rats in both age groups, implying that glymphatic transport, including solute clearance from brain parenchyma, is impaired during evolving hypertension in young SHR, an effect that worsens in states of chronic hypertension. The study demonstrates the suppression of glymphatic clearance in SHR rats and thus offers new insight into the coexistence of hypertension and concomitant vascular pathologies in Alzheimer's disease. The study further highlights the importance of considering the distribution of tracers in the CSF compartment in the analysis of the glymphatic system.

Indexed as

Age FactorsAlzheimer DiseaseAnimalsCerebral VentriclesCerebrospinal FluidContrast MediaDisease ProgressionGlymphatic SystemHeterocyclic CompoundsHypertensionMagnetic Resonance ImagingMaleOrganometallic CompoundsOrgan SizeRatsRats, Inbred SHRContrast Mediagadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetateHeterocyclic CompoundsOrganometallic Compoundscontrast agentCSF transport kineticsmiddle cerebral arteryperivascular spacessmall vessel diseasevolumetric MR

Identifiers

PMID31209176
PMCPMC6687896
OpenAlexW2952584877

What OpenQuestion holds

Textmetadata
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.