Dokument: Flecainide mediated sodium channel blockade enhances blood brain barrier integrity and promotes neuroprotection in neuroinflammation
| Titel: | Flecainide mediated sodium channel blockade enhances blood brain barrier integrity and promotes neuroprotection in neuroinflammation | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=71243 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20251106-103520-1 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Sindi, Mustafa [Autor] Klees, Diana [Autor] Dobelmann, Vera [Autor] Disse, Paul [Autor] Weigel, Hanne [Autor] Lichtenberg, Stefanie [Autor] Ricci, Rebekka [Autor] Thewes, Leonie [Autor] Deniz-Köseoglu, Gülsüm [Autor] Hecker, Christina [Autor] | |||||||
| Dateien: |
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| Stichwörter: | Flecainide , Safinamide , Sodium-channel blocking , Blood-brain-barrier , EAE , Neuroprotection , Rasagiline , MAO-B inhibition , Multiple sclerosis | |||||||
| Beschreibung: | 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. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Sindi, M., Klees, D., Dobelmann, V., Disse, P., Weigel, H., Bock, S., Ricci, R., Thewes, L., Deniz-Köseoglu, G., Hecker, C., Müntefering, T., Issberner, A., Gruchot, J., Hartung, H.-P., Ruck, T., Berndt, C., Kurz, T., Stark, H., Küry, P., … Albrecht, P. (2025). Flecainide mediated sodium channel blockade enhances blood brain barrier integrity and promotes neuroprotection in neuroinflammation. Scientific Reports, 15, Article 31032. https://doi.org/10.1038/s41598-025-15430-w | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 06.11.2025 | |||||||
| Dateien geändert am: | 06.11.2025 |
