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Secondary Degeneration of Oligodendrocyte Precursor Cells Occurs as Early as 24 h after Optic Nerve Injury in Rats

Optic nerve injury causes secondary degeneration, a sequela that spreads damage from the primary injury to adjacent tissue, through mechanisms such as oxidative stress, apoptosis, and blood-brain barrier (BBB) dysfunction. Oligodendrocyte precursor cells (OPCs), a key component of the BBB and oligod...

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Autores principales: Toomey, Lillian M., Papini, Melissa G., Clarke, Thomas O., Wright, Alexander J., Denham, Eleanor, Warnock, Andrew, McGonigle, Terry, Bartlett, Carole A., Fitzgerald, Melinda, Anyaegbu, Chidozie C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964292/
https://www.ncbi.nlm.nih.gov/pubmed/36834873
http://dx.doi.org/10.3390/ijms24043463
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author Toomey, Lillian M.
Papini, Melissa G.
Clarke, Thomas O.
Wright, Alexander J.
Denham, Eleanor
Warnock, Andrew
McGonigle, Terry
Bartlett, Carole A.
Fitzgerald, Melinda
Anyaegbu, Chidozie C.
author_facet Toomey, Lillian M.
Papini, Melissa G.
Clarke, Thomas O.
Wright, Alexander J.
Denham, Eleanor
Warnock, Andrew
McGonigle, Terry
Bartlett, Carole A.
Fitzgerald, Melinda
Anyaegbu, Chidozie C.
author_sort Toomey, Lillian M.
collection PubMed
description Optic nerve injury causes secondary degeneration, a sequela that spreads damage from the primary injury to adjacent tissue, through mechanisms such as oxidative stress, apoptosis, and blood-brain barrier (BBB) dysfunction. Oligodendrocyte precursor cells (OPCs), a key component of the BBB and oligodendrogenesis, are vulnerable to oxidative deoxyribonucleic acid (DNA) damage by 3 days post-injury. However, it is unclear whether oxidative damage in OPCs occurs earlier at 1 day post-injury, or whether a critical ‘window-of-opportunity’ exists for therapeutic intervention. Here, a partial optic nerve transection rat model of secondary degeneration was used with immunohistochemistry to assess BBB dysfunction, oxidative stress, and proliferation in OPCs vulnerable to secondary degeneration. At 1 day post-injury, BBB breach and oxidative DNA damage were observed, alongside increased density of DNA-damaged proliferating cells. DNA-damaged cells underwent apoptosis (cleaved caspase3+), and apoptosis was associated with BBB breach. OPCs experienced DNA damage and apoptosis and were the major proliferating cell type with DNA damage. However, the majority of caspase3+ cells were not OPCs. These results provide novel insights into acute secondary degeneration mechanisms in the optic nerve, highlighting the need to consider early oxidative damage to OPCs in therapeutic efforts to limit degeneration following optic nerve injury.
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spelling pubmed-99642922023-02-26 Secondary Degeneration of Oligodendrocyte Precursor Cells Occurs as Early as 24 h after Optic Nerve Injury in Rats Toomey, Lillian M. Papini, Melissa G. Clarke, Thomas O. Wright, Alexander J. Denham, Eleanor Warnock, Andrew McGonigle, Terry Bartlett, Carole A. Fitzgerald, Melinda Anyaegbu, Chidozie C. Int J Mol Sci Article Optic nerve injury causes secondary degeneration, a sequela that spreads damage from the primary injury to adjacent tissue, through mechanisms such as oxidative stress, apoptosis, and blood-brain barrier (BBB) dysfunction. Oligodendrocyte precursor cells (OPCs), a key component of the BBB and oligodendrogenesis, are vulnerable to oxidative deoxyribonucleic acid (DNA) damage by 3 days post-injury. However, it is unclear whether oxidative damage in OPCs occurs earlier at 1 day post-injury, or whether a critical ‘window-of-opportunity’ exists for therapeutic intervention. Here, a partial optic nerve transection rat model of secondary degeneration was used with immunohistochemistry to assess BBB dysfunction, oxidative stress, and proliferation in OPCs vulnerable to secondary degeneration. At 1 day post-injury, BBB breach and oxidative DNA damage were observed, alongside increased density of DNA-damaged proliferating cells. DNA-damaged cells underwent apoptosis (cleaved caspase3+), and apoptosis was associated with BBB breach. OPCs experienced DNA damage and apoptosis and were the major proliferating cell type with DNA damage. However, the majority of caspase3+ cells were not OPCs. These results provide novel insights into acute secondary degeneration mechanisms in the optic nerve, highlighting the need to consider early oxidative damage to OPCs in therapeutic efforts to limit degeneration following optic nerve injury. MDPI 2023-02-09 /pmc/articles/PMC9964292/ /pubmed/36834873 http://dx.doi.org/10.3390/ijms24043463 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Toomey, Lillian M.
Papini, Melissa G.
Clarke, Thomas O.
Wright, Alexander J.
Denham, Eleanor
Warnock, Andrew
McGonigle, Terry
Bartlett, Carole A.
Fitzgerald, Melinda
Anyaegbu, Chidozie C.
Secondary Degeneration of Oligodendrocyte Precursor Cells Occurs as Early as 24 h after Optic Nerve Injury in Rats
title Secondary Degeneration of Oligodendrocyte Precursor Cells Occurs as Early as 24 h after Optic Nerve Injury in Rats
title_full Secondary Degeneration of Oligodendrocyte Precursor Cells Occurs as Early as 24 h after Optic Nerve Injury in Rats
title_fullStr Secondary Degeneration of Oligodendrocyte Precursor Cells Occurs as Early as 24 h after Optic Nerve Injury in Rats
title_full_unstemmed Secondary Degeneration of Oligodendrocyte Precursor Cells Occurs as Early as 24 h after Optic Nerve Injury in Rats
title_short Secondary Degeneration of Oligodendrocyte Precursor Cells Occurs as Early as 24 h after Optic Nerve Injury in Rats
title_sort secondary degeneration of oligodendrocyte precursor cells occurs as early as 24 h after optic nerve injury in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964292/
https://www.ncbi.nlm.nih.gov/pubmed/36834873
http://dx.doi.org/10.3390/ijms24043463
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