A Novel Ex Vivo Model to Study Therapeutic Treatments for Myelin Repair following Ischemic Damage
Stroke is a major reason for persistent disability due to insufficient treatment strategies beyond reperfusion, leading to oligodendrocyte death and axon demyelination, persistent inflammation and astrogliosis in peri-infarct areas. After injury, oligodendroglial precursor cells (OPCs) have been sho...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/13/10972 |
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| author | Luisa Werner Michael Gliem Nicole Rychlik Goran Pavic Laura Reiche Frank Kirchhoff Markley Silva Oliveira Junior Joel Gruchot Sven G. Meuth Patrick Küry Peter Göttle |
| author_facet | Luisa Werner Michael Gliem Nicole Rychlik Goran Pavic Laura Reiche Frank Kirchhoff Markley Silva Oliveira Junior Joel Gruchot Sven G. Meuth Patrick Küry Peter Göttle |
| author_sort | Luisa Werner |
| collection | DOAJ |
| description | Stroke is a major reason for persistent disability due to insufficient treatment strategies beyond reperfusion, leading to oligodendrocyte death and axon demyelination, persistent inflammation and astrogliosis in peri-infarct areas. After injury, oligodendroglial precursor cells (OPCs) have been shown to compensate for myelin loss and prevent axonal loss through the replacement of lost oligodendrocytes, an inefficient process leaving axons chronically demyelinated. Phenotypic screening approaches in demyelinating paradigms revealed substances that promote myelin repair. We established an ex vivo adult organotypic coronal slice culture (OCSC) system to study repair after stroke in a resource-efficient way. Post-photothrombotic OCSCs can be manipulated for 8 d by exposure to pharmacologically active substances testing remyelination activity. OCSCs were isolated from a NG2-CreERT2-td-Tomato knock-in transgenic mouse line to analyze oligodendroglial fate/differentiation and kinetics. Parbendazole boosted differentiation of NG2<sup>+</sup> cells and stabilized oligodendroglial fate reflected by altered expression of associated markers PDGFR-α, CC1, BCAS1 and Sox10 and GFAP. In vitro scratch assay and chemical ischemia confirmed the observed effects upon parbendazole treatment. Adult OCSCs represent a fast, reproducible, and quantifiable model to study OPC differentiation competence after stroke. Pharmacological stimulation by means of parbendazole promoted OPC differentiation. |
| first_indexed | 2024-03-11T01:39:19Z |
| format | Article |
| id | doaj.art-b0044b3c8a434953aee6d908cddc56f1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:39:19Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b0044b3c8a434953aee6d908cddc56f12023-11-18T16:46:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131097210.3390/ijms241310972A Novel Ex Vivo Model to Study Therapeutic Treatments for Myelin Repair following Ischemic DamageLuisa Werner0Michael Gliem1Nicole Rychlik2Goran Pavic3Laura Reiche4Frank Kirchhoff5Markley Silva Oliveira Junior6Joel Gruchot7Sven G. Meuth8Patrick Küry9Peter Göttle10Department of Neurology, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, GermanyMolecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, 66424 Homburg, GermanyDepartment of Neurology, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, GermanyStroke is a major reason for persistent disability due to insufficient treatment strategies beyond reperfusion, leading to oligodendrocyte death and axon demyelination, persistent inflammation and astrogliosis in peri-infarct areas. After injury, oligodendroglial precursor cells (OPCs) have been shown to compensate for myelin loss and prevent axonal loss through the replacement of lost oligodendrocytes, an inefficient process leaving axons chronically demyelinated. Phenotypic screening approaches in demyelinating paradigms revealed substances that promote myelin repair. We established an ex vivo adult organotypic coronal slice culture (OCSC) system to study repair after stroke in a resource-efficient way. Post-photothrombotic OCSCs can be manipulated for 8 d by exposure to pharmacologically active substances testing remyelination activity. OCSCs were isolated from a NG2-CreERT2-td-Tomato knock-in transgenic mouse line to analyze oligodendroglial fate/differentiation and kinetics. Parbendazole boosted differentiation of NG2<sup>+</sup> cells and stabilized oligodendroglial fate reflected by altered expression of associated markers PDGFR-α, CC1, BCAS1 and Sox10 and GFAP. In vitro scratch assay and chemical ischemia confirmed the observed effects upon parbendazole treatment. Adult OCSCs represent a fast, reproducible, and quantifiable model to study OPC differentiation competence after stroke. Pharmacological stimulation by means of parbendazole promoted OPC differentiation.https://www.mdpi.com/1422-0067/24/13/10972ischemic strokeneuroregenerationmyelin repairoligodendrocyte |
| spellingShingle | Luisa Werner Michael Gliem Nicole Rychlik Goran Pavic Laura Reiche Frank Kirchhoff Markley Silva Oliveira Junior Joel Gruchot Sven G. Meuth Patrick Küry Peter Göttle A Novel Ex Vivo Model to Study Therapeutic Treatments for Myelin Repair following Ischemic Damage International Journal of Molecular Sciences ischemic stroke neuroregeneration myelin repair oligodendrocyte |
| title | A Novel Ex Vivo Model to Study Therapeutic Treatments for Myelin Repair following Ischemic Damage |
| title_full | A Novel Ex Vivo Model to Study Therapeutic Treatments for Myelin Repair following Ischemic Damage |
| title_fullStr | A Novel Ex Vivo Model to Study Therapeutic Treatments for Myelin Repair following Ischemic Damage |
| title_full_unstemmed | A Novel Ex Vivo Model to Study Therapeutic Treatments for Myelin Repair following Ischemic Damage |
| title_short | A Novel Ex Vivo Model to Study Therapeutic Treatments for Myelin Repair following Ischemic Damage |
| title_sort | novel ex vivo model to study therapeutic treatments for myelin repair following ischemic damage |
| topic | ischemic stroke neuroregeneration myelin repair oligodendrocyte |
| url | https://www.mdpi.com/1422-0067/24/13/10972 |
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