Evidence map›Paper›PMID 36068581›Full record

ArticleFluids and barriers of the CNS2022

Lysophosphatidic acid as a CSF lipid in posthemorrhagic hydrocephalus that drives CSF accumulation via TRPV4-induced hyperactivation of NKCC1.

Trine L Toft-Bertelsen, Dagne Barbuskaite, Eva Kjer Heerfordt, Sara Diana Lolansen, Søren Norge Andreassen, Nina Rostgaard, Markus Harboe Olsen, Nicolas H Norager, Tenna Capion, Martin Fredensborg Rath and 2 more

Open access · goldAbstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
8.4field-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

55 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.

  1. Pooled it
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  19. The NaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  20. Metabolomic and lipidomic pathways in aneurysmal subarachnoid hemorrhage.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
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

12 authors at 2 institutions in 1 country.

Trine L Toft-BertelsenDepartment of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.
Dagne BarbuskaiteDepartment of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.
Eva Kjer HeerfordtDepartment of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.
Sara Diana LolansenDepartment of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.
Søren Norge AndreassenDepartment of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.
Nina RostgaardDepartment of Neurosurgery, Neuroscience Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Markus Harboe OlsenDepartment of Neuroanaesthesiology, Neuroscience Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Nicolas H NoragerDepartment of Neurosurgery, Neuroscience Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Tenna CapionDepartment of Neurosurgery, Neuroscience Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Martin Fredensborg RathDepartment of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.
Marianne JuhlerDepartment of Neurosurgery, Neuroscience Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Nanna MacAulayDepartment of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark. macaulay@sund.ku.dk.ORCID http://orcid.org/0000-0002-7800-6600
University of Copenhagen · DKCopenhagen University Hospital · DK

Funding

Lundbeckfonden R276-2018-403Lundbeckfonden R303-2018-3005the Carlsberg Foundation CF19-0056the Novo Nordic Foundation NNF17OC0024718the Research Council at Copenhagen University Hospital Rigshospitalet E-23565-03
6 · The paper itself

Abstract

backgroundA range of neurological pathologies may lead to secondary hydrocephalus. Treatment has largely been limited to surgical cerebrospinal fluid (CSF) diversion, as specific and efficient pharmacological options are lacking, partly due to the elusive molecular nature of the CSF secretion apparatus and its regulatory properties in physiology and pathophysiology.

methodsCSF obtained from patients with subarachnoid hemorrhage (SAH) and rats with experimentally inflicted intraventricular hemorrhage (IVH) was analyzed for lysophosphatidic acid (LPA) by alpha-LISA. We employed the in vivo rat model to determine the effect of LPA on ventricular size and brain water content, and to reveal the effect of activation and inhibition of the transient receptor potential vanilloid 4 (TRPV4) ion channel on intracranial pressure and CSF secretion rate. LPA-mediated modulation of TRPV4 was determined with electrophysiology and an ex vivo radio-isotope assay was employed to determine the effect of these modulators on choroid plexus transport.

resultsElevated levels of LPA were observed in CSF obtained from patients with subarachnoid hemorrhage (SAH) and from rats with experimentally-inflicted intraventricular hemorrhage (IVH). Intraventricular administration of LPA caused elevated brain water content and ventriculomegaly in experimental rats, via its action as an agonist of the choroidal transient receptor potential vanilloid 4 (TRPV4) channel. TRPV4 was revealed as a novel regulator of ICP in experimental rats via its ability to modulate the CSF secretion rate through its direct activation of the Na

conclusionsTogether, our data reveal that a serum lipid present in brain pathologies with hemorrhagic events promotes CSF hypersecretion and ensuing brain water accumulation via its direct action on TRPV4 and its downstream regulation of NKCC1. TRPV4 may therefore be a promising future pharmacological target for pathologies involving brain water accumulation.

Indexed as

HydrocephalusSubarachnoid HemorrhageAnimalsCerebral HemorrhageLysophospholipidsRatsTRPV Cation ChannelsWaterlysophosphatidic acidLysophospholipidsTrpv4 protein, ratTRPV Cation ChannelsWaterBrain waterCerebrospinal fluidChoroid plexusIntraventricular hemorrhageIVHLPAMembrane transportSAHSubarachnoid hemorrhageTransient receptor potential vanilloid 4

Identifiers

PMID36068581
PMCPMC9450297
OpenAlexW4294817527

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.