{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:24:08Z","timestamp":1789687448227,"version":"4.0.1"},"reference-count":45,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research","doi-asserted-by":"publisher","award":["APP1160691"],"award-info":[{"award-number":["APP1160691"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MS Research Australia Postgraduate Scholarship","award":["APP1160691"],"award-info":[{"award-number":["APP1160691"]}]},{"name":"Perron Institute for Neurological and Translational Science","award":["APP1160691"],"award-info":[{"award-number":["APP1160691"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u2018window-of-opportunity\u2019 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.<\/jats:p>","DOI":"10.3390\/ijms24043463","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T02:32:07Z","timestamp":1675909927000},"page":"3463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Secondary Degeneration of Oligodendrocyte Precursor Cells Occurs as Early as 24 h after Optic Nerve Injury in Rats"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9435-6128","authenticated-orcid":false,"given":"Lillian M.","family":"Toomey","sequence":"first","affiliation":[{"name":"Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia"},{"name":"Perron Institute for Neurological and Translational Science, Sarich Neuroscience Research Institute Building, 8 Verdun St., Nedlands, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa G.","family":"Papini","sequence":"additional","affiliation":[{"name":"Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas O.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Wright","sequence":"additional","affiliation":[{"name":"Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Denham","sequence":"additional","affiliation":[{"name":"Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Warnock","sequence":"additional","affiliation":[{"name":"Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry","family":"McGonigle","sequence":"additional","affiliation":[{"name":"Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole A.","family":"Bartlett","sequence":"additional","affiliation":[{"name":"Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4823-8179","authenticated-orcid":false,"given":"Melinda","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia"},{"name":"Perron Institute for Neurological and Translational Science, Sarich Neuroscience Research Institute Building, 8 Verdun St., Nedlands, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0618-3173","authenticated-orcid":false,"given":"Chidozie C.","family":"Anyaegbu","sequence":"additional","affiliation":[{"name":"Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia"},{"name":"Perron Institute for Neurological and Translational Science, Sarich Neuroscience Research Institute Building, 8 Verdun St., Nedlands, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/bja\/aem131","article-title":"Pathophysiology of Traumatic Brain Injury","volume":"99","author":"Werner","year":"2007","journal-title":"Br. 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