Al-Griw, M.A., Salter, M.G. and Wood, I.C. orcid.org/0000-0003-1886-2533 (2022) Blocking of NF‑kB/p38 MAPK pathways mitigates oligodendrocyte pathology in a model of neonatal white matter injury. Acta Neurobiologiae Experimentalis, 82 (1). pp. 52-64. ISSN 0065-1400
Abstract
Reactive gliosis and inflammation are risk factors for white matter injury (WMI) development, which are correlated with the development of many neurodevelopmental deficits with no treatment. This study aimed to understand the mechanisms correlated with WMI, with a particular focus on the role of nuclear factor‑kappa B (NF‑kB) and p38 mitogen‑activated protein kinases (MAPKs) pathways. Seven‑day‑old Wistar rats were used to generate cerebellar tissue slices. Slices were cultured and randomly allocated to one of 3 groups and treated as follows: group‑I (control); group‑II (WMI), slices were subjected to 20 min of oxygen‑glucose deprivation (OGD); group‑III (WMI+ blockers), slices were subjected to OGD and treated with the blockers. Results showed that OGD insult triggered a marked increase in the apoptosis among WM elements, as confirmed by TUNEL assay. Immunocytochemical experiments revealed that there was a significant decrease in the percent of MBP+ OLs and NG2+ OPCs, and myelin integrity. There was also a significant increase in the percent of reactive microglia and astrocytes. BrdU immunostaining revealed there was an increase in the percent of proliferating microglia and astrocytes. Q‑RT‑PCR results showed OGD upregulated the expression levels of cytokines (TNF‑α, IL‑1, IL‑6, and IL‑1β) and inducible nitric oxide synthase (iNOS). On the other hand, treatment with BAY11 or SB203580 significantly enhanced the OL survival, restored myelin loss, and reduced microglia and astrocyte reactivity, and downregulated the iNOS and cytokine expression. Our findings demonstrate that blocking of NF‑KB/p38 MAPK pathways alleviated reactive gliosis, inflammation, and OL loss upon WMI. The findings may help to develop therapeutic interventions for WMI.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Copyright © 2022 Acta Neurobiologiae Experimentalis. This work is licensed under a Creative Commons Attribution 4.0 International License. |
Keywords: | white matter, NF‑KB, p38 MAPK, reactive gliosis, astrocytes, microglia, inflammation, cytokines, iNOS |
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: | 05 Dec 2024 14:54 |
Last Modified: | 05 Dec 2024 17:01 |
Published Version: | https://ane.pl/index.php/ane/article/view/2327 |
Status: | Published |
Publisher: | The Nencki Institute of Experimental Biology, Polish Academy of Sciences |
Identification Number: | 10.55782/ane-2022-005 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:220424 |