Evidence map›Paper›PMID 32036791›Full record

ArticleFluids and barriers of the CNS2020

Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage.

Lilla Barna, Fruzsina R Walter, András Harazin, Alexandra Bocsik, András Kincses, Vilmos Tubak, Katalin Jósvay, Ágnes Zvara, Patricia Campos-Bedolla, Mária A Deli

Open access · goldAbstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

21 citing papers in PubMed, 36 citations in OpenAlex.

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  13. Effects of fasudil on blood-brain barrier integrity.Fluids and barriers of the CNS · 2022
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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

10 authors at 3 institutions in 2 countries.

Lilla BarnaInstitute of Biophysics, Biological Research Centre, Temesvári krt. 62, Szeged, 6726, Hungary.
Fruzsina R WalterInstitute of Biophysics, Biological Research Centre, Temesvári krt. 62, Szeged, 6726, Hungary.ORCID http://orcid.org/0000-0001-8145-2823
András HarazinInstitute of Biophysics, Biological Research Centre, Temesvári krt. 62, Szeged, 6726, Hungary.ORCID http://orcid.org/0000-0002-0904-5606
Alexandra BocsikInstitute of Biophysics, Biological Research Centre, Temesvári krt. 62, Szeged, 6726, Hungary.
András KincsesInstitute of Biophysics, Biological Research Centre, Temesvári krt. 62, Szeged, 6726, Hungary.
Vilmos TubakCreative Laboratory Ltd., Temesvári krt. 62, Szeged, 6726, Hungary.ORCID http://orcid.org/0000-0002-6141-3920
Katalin JósvayInstitute of Biochemistry, Biological Research Centre, Temesvári krt. 62, Szeged, 6726, Hungary.
Ágnes ZvaraInstitute of Genetics, Biological Research Centre, Temesvári krt. 62, Szeged, 6726, Hungary.
Patricia Campos-BedollaUnidad de Investigacion Medica en Enfermedades Neurologicas, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, 06720, Ciudad de México, DF, México.ORCID http://orcid.org/0000-0002-8177-0511
Mária A DeliInstitute of Biophysics, Biological Research Centre, Temesvári krt. 62, Szeged, 6726, Hungary. deli.maria@brc.hu.ORCID http://orcid.org/0000-0001-6084-6524
HUN-REN Szegedi Biológiai Kutatóközpont · HUUniversity of Szeged · HUMexican Social Security Institute · MX

Funding

Bilateral Program CONACYT 193490-2012Innovációs és Technológiai Minisztérium ÚNKP-19-SZTE42Magyar Tudományos Akadémia Bolyai fellowshipMagyar Tudományos Akadémia NKM-51/2014Nemzeti Kutatási Fejlesztési és Innovációs Hivatal OTKA PD-128480
6 · The paper itself

Abstract

backgroundExcitotoxicity is a central pathological pathway in many neurological diseases with blood-brain barrier (BBB) dysfunction. Kainate, an exogenous excitotoxin, induces epilepsy and BBB damage in animal models, but the direct effect of kainate on brain endothelial cells has not been studied in detail. Our aim was to examine the direct effects of kainate on cultured cells of the BBB and to test three anti-inflammatory and antioxidant drugs used in clinical practice, simvastatin, edaravone and dexamethasone, to protect against kainate-induced changes.

methodsPrimary rat brain endothelial cell, pericyte and astroglia cultures were used to study cell viability by impedance measurement. BBB permeability was measured on a model made from the co-culture of the three cell types. The production of nitrogen monoxide and reactive oxygen species was followed by fluorescent probes. The mRNA expression of kainate receptors and nitric oxide synthases were studied by PCR.

resultsKainate damaged brain endothelial cells and made the immunostaining of junctional proteins claudin-5 and zonula occludens-1 discontinuous at the cell border indicating the opening of the barrier. The permeability of the BBB model for marker molecules fluorescein and albumin and the production of nitric oxide in brain endothelial cells were increased by kainate. Simvastatin, edaravone and dexamethasone protected against the reduced cell viability, increased permeability and the morphological changes in cellular junctions caused by kainate. Dexamethasone attenuated the elevated nitric oxide production and decreased the inducible nitric oxide synthase (NOS2/iNOS) mRNA expression increased by kainate treatment.

conclusionKainate directly damaged cultured brain endothelial cells. Simvastatin, edaravone and dexamethasone protected the BBB model against kainate-induced changes. Our results confirmed the potential clinical usefulness of these drugs to attenuate BBB damage.

Indexed as

AnimalsBlood-Brain BarrierBrainCapillary PermeabilityEdaravoneEndothelial CellsNitric OxidePermeabilityRatsSimvastatinEdaravoneNitric OxideSimvastatinBlood–brain barrierBrain endothelial cellsDexamethasoneEdaravoneKainateNitric oxide synthasePermeabilityReactive oxygen speciesSimvastatin

Identifiers

PMID32036791
PMCPMC7008534
OpenAlexW3008362954

What OpenQuestion holds

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LicenceCC BY
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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.