{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:44:09Z","timestamp":1791996249493,"version":"4.4.0"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian Government Research Training Program Scholarship","award":["APP2016688"],"award-info":[{"award-number":["APP2016688"]}]},{"name":"Australian Government Research Training Program Scholarship","award":["GNT2008793"],"award-info":[{"award-number":["GNT2008793"]}]},{"name":"National Health and Medical Research Council Investigator funding","award":["APP2016688"],"award-info":[{"award-number":["APP2016688"]}]},{"name":"National Health and Medical Research Council Investigator funding","award":["GNT2008793"],"award-info":[{"award-number":["GNT2008793"]}]},{"name":"Victorian Government\u2019s Operational Infrastructure Support Program","award":["APP2016688"],"award-info":[{"award-number":["APP2016688"]}]},{"name":"Victorian Government\u2019s Operational Infrastructure Support Program","award":["GNT2008793"],"award-info":[{"award-number":["GNT2008793"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Blood\u2013brain barrier (BBB) dysfunction and neuroinflammation are key mechanisms of brain injury. We performed a time-course study following neonatal hypoxia\u2013ischemia (HI) to characterize these events. HI brain injury was induced in postnatal day 10 rats by single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). At 6, 12, 24, and 72 h (h) post-HI, brains were collected to assess neuropathology and BBB dysfunction. A significant breakdown of the BBB was observed in the HI injury group compared to the sham group from 6 h in the cortex and hippocampus (p &lt; 0.001), including a significant increase in albumin extravasation (p &lt; 0.0033) and decrease in basal lamina integrity and tight-junction proteins. There was a decrease in resting microglia (p &lt; 0.0001) transitioning to an intermediate state from as early as 6 h post-HI, with the intermediate microglia peaking at 12 h (p &lt; 0.0001), which significantly correlated to the peak of microbleeds. Neonatal HI insult leads to significant brain injury over the first 72 h that is mediated by BBB disruption within 6 h and a transitioning state of the resident microglia. Key BBB events coincide with the appearance of the intermediate microglial state and this relationship warrants further research and may be a key target for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/cells13080660","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T10:08:50Z","timestamp":1712657330000},"page":"660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The Temporal Relationship between Blood\u2013Brain Barrier Integrity and Microglial Response following Neonatal Hypoxia Ischemia"],"prefix":"10.3390","volume":"13","author":[{"given":"Arya","family":"Jithoo","sequence":"first","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayla R.","family":"Penny","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen","family":"Pham","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4807-2340","authenticated-orcid":false,"given":"Amy E.","family":"Sutherland","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2971-9484","authenticated-orcid":false,"given":"Madeleine J.","family":"Smith","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Petraki","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Fahey","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Monash University, Melbourne, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Jenkin","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9664-4182","authenticated-orcid":false,"given":"Atul","family":"Malhotra","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia"},{"name":"Department of Paediatrics, Monash University, Melbourne, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne L.","family":"Miller","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8421-461X","authenticated-orcid":false,"given":"Courtney A.","family":"McDonald","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.nbd.2008.08.005","article-title":"Blood-brain barrier tight junction permeability and ischemic stroke","volume":"32","author":"Sandoval","year":"2008","journal-title":"Neurobiol. 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