Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage
Abstract Background 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...
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| Format: | Article |
| Language: | English |
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BMC
2020-02-01
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| Series: | Fluids and Barriers of the CNS |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12987-019-0166-1 |
| _version_ | 1831813823569330176 |
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| author | Lilla Barna Fruzsina R. Walter András Harazin Alexandra Bocsik András Kincses Vilmos Tubak Katalin Jósvay Ágnes Zvara Patricia Campos-Bedolla Mária A. Deli |
| author_facet | Lilla Barna Fruzsina R. Walter András Harazin Alexandra Bocsik András Kincses Vilmos Tubak Katalin Jósvay Ágnes Zvara Patricia Campos-Bedolla Mária A. Deli |
| author_sort | Lilla Barna |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusion 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. |
| first_indexed | 2024-12-22T22:03:20Z |
| format | Article |
| id | doaj.art-8004acb906cf4c54a425795c5e55d59e |
| institution | Directory Open Access Journal |
| issn | 2045-8118 |
| language | English |
| last_indexed | 2024-12-22T22:03:20Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Fluids and Barriers of the CNS |
| spelling | doaj.art-8004acb906cf4c54a425795c5e55d59e2022-12-21T18:11:04ZengBMCFluids and Barriers of the CNS2045-81182020-02-0117111310.1186/s12987-019-0166-1Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damageLilla Barna0Fruzsina R. Walter1András Harazin2Alexandra Bocsik3András Kincses4Vilmos Tubak5Katalin Jósvay6Ágnes Zvara7Patricia Campos-Bedolla8Mária A. Deli9Institute of Biophysics, Biological Research CentreInstitute of Biophysics, Biological Research CentreInstitute of Biophysics, Biological Research CentreInstitute of Biophysics, Biological Research CentreInstitute of Biophysics, Biological Research CentreCreative Laboratory Ltd.Institute of Biochemistry, Biological Research CentreInstitute of Genetics, Biological Research CentreUnidad de Investigacion Medica en Enfermedades Neurologicas, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro SocialInstitute of Biophysics, Biological Research CentreAbstract Background 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. Methods 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. Results 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. Conclusion 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.https://doi.org/10.1186/s12987-019-0166-1Blood–brain barrierBrain endothelial cellsKainateSimvastatinEdaravoneDexamethasone |
| spellingShingle | Lilla Barna Fruzsina R. Walter András Harazin Alexandra Bocsik András Kincses Vilmos Tubak Katalin Jósvay Ágnes Zvara Patricia Campos-Bedolla Mária A. Deli Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage Fluids and Barriers of the CNS Blood–brain barrier Brain endothelial cells Kainate Simvastatin Edaravone Dexamethasone |
| title | Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage |
| title_full | Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage |
| title_fullStr | Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage |
| title_full_unstemmed | Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage |
| title_short | Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage |
| title_sort | simvastatin edaravone and dexamethasone protect against kainate induced brain endothelial cell damage |
| topic | Blood–brain barrier Brain endothelial cells Kainate Simvastatin Edaravone Dexamethasone |
| url | https://doi.org/10.1186/s12987-019-0166-1 |
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