Al-Griw, MA, Salter, MG and Wood, IC orcid.org/0000-0003-1886-2533 (2021) Inhibition of ionotropic GluR signaling preserves oligodendrocyte lineage and myelination in an ex vivo rat model of white matter ischemic injury. Acta Neurobiologiae Experimentalis, 81 (3). pp. 233-248. ISSN 0065-1400
Abstract
Preterm infants have a high risk of neonatal white matter injury (WMI). WMI leads to reduced myelination, inflammation, and clinical neurodevelopmental deficits for which there are no effective treatments. Ionotropic glutamate receptor (iGluR) induced excitotoxicity contributes to oligodendrocyte (OL) lineage cell loss and demyelination in brain models of neonatal and adult WMI. Here, we hypothesized that simulated ischemia (oxygen–glucose deprivation) damages white matter via activation of iGluR signaling, and that iGluR inhibition shortly after WMI could mitigate OL loss, enhance myelination, and suppress inflammation in an ex vivo cerebellar slice model of developing WMI. Inhibition of iGluR signaling by a combined block of AMPA and NMDA receptors, shortly after simulated ischemia, restored myelination, reduced apoptotic OLs, and enhanced OL precursor cell proliferation and maturation as well as upregulated expression of transcription factors regulating OL development and remyelination. Our findings demonstrate that iGluR inhibition post–injury alleviates OL lineage cell loss and inflammation and promotes myelination upon developing WMI. The findings may help to develop therapeutic interventions for the WMI treatment.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 by Acta Neurobiologiae Experimentalis. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY). |
Keywords: | neonatal white matter injury, ischemia, ionotropic glutamate receptors, oligodendrocytes, oligodendrocyte precursors |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 06 Dec 2021 14:16 |
Last Modified: | 06 Dec 2021 14:16 |
Status: | Published |
Publisher: | Nencki Institute of Experimental Biology and Polish Neuroscience Society, PTBUN |
Identification Number: | 10.21307/ane-2021-022 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:181191 |