Evidence map›Paper›PMID 40849530›Full record

ArticleScientific reports2025

Flecainide mediated sodium channel blockade enhances blood brain barrier integrity and promotes neuroprotection in neuroinflammation.

Mustafa Sindi, Diana Klees, Vera Dobelmann, Paul Disse, Hanne Weigel, Stefanie Lichtenberg, Rebekka Ricci, Leonie Thewes, Gülsüm Deniz-Köseoglu, Christina Hecker and 14 more

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Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

24 authors.

Mustafa SindiDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Diana KleesDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Vera DobelmannDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Paul DisseDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Hanne WeigelDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Stefanie LichtenbergDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Rebekka RicciTheodor Kocher Institute, University of Bern, Bern, Switzerland.
Leonie ThewesDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Gülsüm Deniz-KöseogluDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Christina HeckerDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Thomas MünteferingDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Andrea IssbernerDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Joel GruchotDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Hans-Peter HartungDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Tobias RuckDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Carsten BerndtDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Thomas KurzInstitute of Pharmaceutical and Medical Chemistry, Faculty of Mathematics and Natural Sciences, Heinrich-Heine University, Düsseldorf, Germany.
Holger StarkInstitute of Pharmaceutical and Medical Chemistry, Faculty of Mathematics and Natural Sciences, Heinrich-Heine University, Düsseldorf, Germany.
Patrick KüryDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Britta EngelhardtTheodor Kocher Institute, University of Bern, Bern, Switzerland.
Ruth LyckTheodor Kocher Institute, University of Bern, Bern, Switzerland.
Sven G MeuthDepartment of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Michael Dietrich *Department of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Philipp Albrecht *Department of Neurology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany. phil.albrecht@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multiple Sclerosis (MS), an autoimmune disorder, is characterized by severe neuroinflammation, leading to demyelination and neuronal damage in the CNS, resulting in significant clinical impairment. MS progression involves complex pathological processes like immune cell invasion and cytokine-mediated recruitment to the CNS. Experimental autoimmune encephalomyelitis (EAE), widely used as a model for MS, despite its translational limitations, has been crucial for identifying effective treatments. Recent studies have shown that sodium channel (NaV) blockers and monoamine oxidase- (MAO) B inhibitors can alleviate symptoms of EAE and optic neuritis (ON), but their mode of action remains partially unclear. To evaluate the effects and understand the action mechanism of NaV blockers and MAO-B inhibitors (rasagiline, safinamide, flecainide and phenytoin) in neurological conditions, various techniques were used, including optical coherence tomography (OCT), optomotor response measurement (OMR), flow cytometry, histological evaluations, Evans blue assay, blood-brain barrier (BBB) permeability assay, western blot, proliferations assay, and gene expression analyses. The study found that the primary therapeutic effect comes from inhibiting the NaV 1.5 sodium channel, not MAO-B inhibition. Flecainide, a NaV 1.5 channel blocker, significantly reduced EAE disability scores, mitigated neurodegeneration, preserved visual function, and restricted immune cell migration into the CNS. Importantly, blocking the NaV 1.5 channel had an effect on the BBB, limiting lymphocyte entry into the CNS. This research highlights sodium channel blockers' potential in treating EAE. The findings demonstrate induced neuroprotection and reduced disease progression, suggesting a novel therapeutic approach. Crucially, it reveals for the first time that NaV 1.5 channel blockade leads to neuroprotection primarily by affecting the BBB, a key factor in controlling immune cell migration, thus addressing a critical aspect of neuroinflammation.

Indexed as

Blood-Brain BarrierEncephalomyelitis, Autoimmune, ExperimentalFlecainideNeuroinflammatory DiseasesNeuroprotectionNeuroprotective AgentsSodium Channel BlockersAnimalsFemaleMiceMice, Inbred C57BLMonoamine Oxidase InhibitorsFlecainideMonoamine Oxidase InhibitorsNeuroprotective AgentsSodium Channel BlockersBlood-brain-barrierEAEFlecainideMAO-B inhibitionMultiple sclerosisNeuroprotectionRasagilineSafinamideSodium-channel blocking

Identifiers

PMID40849530
PMCPMC12375043

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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.