{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:37:49Z","timestamp":1760060269086,"version":"build-2065373602"},"reference-count":66,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Neurological Foundation of New Zealand First Postdoctoral Fellowship","award":["2001 FFE","1121013","1323001"],"award-info":[{"award-number":["2001 FFE","1121013","1323001"]}]},{"DOI":"10.13039\/501100001511","name":"Auckland Medical Research Foundation (AMRF)","doi-asserted-by":"publisher","award":["2001 FFE","1121013","1323001"],"award-info":[{"award-number":["2001 FFE","1121013","1323001"]}],"id":[{"id":"10.13039\/501100001511","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001511","name":"AMRF Postdoctoral Fellowship","doi-asserted-by":"publisher","award":["2001 FFE","1121013","1323001"],"award-info":[{"award-number":["2001 FFE","1121013","1323001"]}],"id":[{"id":"10.13039\/501100001511","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perinatal hypoxic\u2013ischemic encephalopathy (HIE) is a condition resulting from oxygen deprivation around the time of birth and may be associated with death, brain damage, and disability. Alongside this, studies have shown that HIE may result in visual impairment. Previously, this was thought to be due to damage to the visual pathways in the brain, in a condition known as cerebral visual impairment. However, recent studies suggest that direct injury to the retina may occur after HIE. Of note, the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome is thought to play a role in perpetuating inflammatory damage in the brain after hypoxia\u2013ischemia (HI). As such, this study aimed to characterize retinal inflammation and the role of the NLRP3 inflammasome after HI using a modified Rice-Vannucci model in postnatal day 10 (P10) rat. Eighteen Sprague-Dawley rats were allocated evenly to three groups. Two groups received surgery to ligate the right common-carotid artery and induce HI, while another group received only sham surgery. Rats exposed to HI received subcutaneous injections of tonabersat (HI + Ton) or saline (HI + vehicle) at 1, 24 and 48 h after HI, and were culled at P17 for analysis. The results showed that the protein expression of GFAP, Iba-1, NLRP3, caspase-1 and connexin43 increased in the retina at 7 d after HI-vehicle compared with sham surgery, much more so in the ipsilateral = than the contralateral retina. Furthermore, = inflammasome components NLRP3, cleaved caspase-1 and connexin43 were significantly upregulated in the ipsilateral retina following HI-vehicle compared to the sham surgery group. Treatment with a connexin43 hemichannel blocker, tonabersat, significantly decreased the expression of the inflammasome markers, cleaved caspase-1 and connexin43, and diminished Iba-1+ cell infiltration in the ipsilateral retina. These findings suggest that direct retinal damage and inflammation may occur after HI. Furthermore, these inflammatory changes are likely mediated and propagated by activation of the NLRP3 inflammasome. Importantly, inhibition of the inflammasome by tonabersat may be able to inhibit retinal inflammation and damage, potentially preventing visual impairment after HI. Further investigation in humans is required to determine the efficacy of tonabersat in treating hypoxic\u2013ischemic injuries to the brain and eye.<\/jats:p>","DOI":"10.3390\/ijms26167996","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T11:41:41Z","timestamp":1755603701000},"page":"7996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tonabersat Inhibits Retinal Inflammation After Hypoxia\u2013Ischemia in the Neonatal Rat"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9366-4882","authenticated-orcid":false,"given":"Jack Jonathan","family":"Maran","sequence":"first","affiliation":[{"name":"Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5062-9849","authenticated-orcid":false,"given":"Alice","family":"McDouall","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1377-0878","authenticated-orcid":false,"given":"Justin M.","family":"Dean","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Davidson","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Odunayo O.","family":"Mugisho","sequence":"additional","affiliation":[{"name":"Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/B978-0-444-64029-1.00010-2","article-title":"Neonatal encephalopathy and hypoxic-ischemic encephalopathy","volume":"162","author":"Gunn","year":"2019","journal-title":"Handb. 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