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

Barna, Lilla and Walter, Fruzsina and Harazin, András and Bocsik, Alexandra and Kincses, András and Jósvay, Katalin and Zvara, Ágnes and Deli, Mária Anna (2020) Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage. Fluids and Barriers of the CNS, 17 (1). ISSN 2045-8118

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Abstract

Excitotoxicity 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.Primary 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.Kainate 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.Kainate 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.

Item Type: Article
Additional Information: Institute of Biophysics, Biological Research Centre, Temesvári krt. 62, Szeged, 6726, Hungary Doctoral School in Biology, University of Szeged, Somogyi u. 4, Szeged, 6720, Hungary Creative Laboratory Ltd., Temesvári krt. 62, Szeged, 6726, Hungary Institute of Biochemistry, Biological Research Centre, Temesvári krt. 62, Szeged, 6726, Hungary Institute of Genetics, Biological Research Centre, Temesvári krt. 62, Szeged, 6726, Hungary Unidad de Investigacion Medica en Enfermedades Neurologicas, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano Del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Ciudad de México, DF, 06720, Mexico Department of Cell Biology and Molecular Medicine, University of Szeged, Szeged, Hungary Export Date: 2 March 2020 Correspondence Address: Deli, M.A.; Institute of Biophysics, Biological Research Centre, Temesvári krt. 62, Hungary; email: deli.maria@brc.hu
Uncontrolled Keywords: DEXAMETHASONE; Permeability; Blood-Brain Barrier; Reactive oxygen species; nitric oxide synthase; SIMVASTATIN; kainate; Edaravone; Brain endothelial cells;
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 28 Sep 2020 13:45
Last Modified: 28 Sep 2020 13:45
URI: http://real.mtak.hu/id/eprint/115154

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