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A Novel Ex Vivo Model to Study Therapeutic Treatments for Myelin Repair following Ischemic Damage

Authors :
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
Source :
International Journal of Molecular Sciences, Vol 24, Iss 13, p 10972 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

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+ 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.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
24
Issue :
13
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.b0044b3c8a434953aee6d908cddc56f1
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms241310972