{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:58:50Z","timestamp":1762102730385,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,10]],"date-time":"2022-04-10T00:00:00Z","timestamp":1649548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["1R21NS095130","1R21NS096525","R44 NS084575","2R01HD057100"],"award-info":[{"award-number":["1R21NS095130","1R21NS096525","R44 NS084575","2R01HD057100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Exposure to hypoxic-ischemic (HI) insults in newborns can predispose them to severe neurological sequela. The mechanisms underlying HI-related brain injury have not been completely elucidated. The neurovascular unit (NVU) is a composite of structures that protect the brain from the influx of detrimental molecules. Changes in the NVU after HI are important because they could reveal endogenous neuroprotective pathways in the cerebral microvasculature. Furthermore, the time course of changes in the NVU after exposure to HI in the newborn remains to be determined. In this study, we examined the effects of severe HI on the time course of changes in the NVU in neonatal rats. Brains were collected from rats exposed to right carotid artery ligation and 2 h of hypoxia on postnatal day 7 with recovery for 6 or 48 h after exposure to sham treatment (Sham) or HI. The right HI and left hypoxic alone sides of the brains were examined by quantitative immunohistochemistry for vascular density (laminin), pericyte vascular coverage (PDGFR\u03b2), astrocyte vascular coverage (GFAP), and claudin-5 expression in the microvasculature of the cerebral cortex, white matter, and hippocampus. HI-related brain injury in neonatal rats was associated with increases in vascular density in the cortex and hippocampus 48 h after HI as well as neurovascular remodeling, including loss of pericyte coverage in the cortex and increases in claudin-5 in the hippocampus 6 h after HI. Astrocyte coverage was not affected by HI injury. The time course of the responses in the different components of the NVU varied after exposure to HI. There were also differential regional responses in the elements of the NVU in response to HI and hypoxia alone.<\/jats:p>","DOI":"10.3390\/ijms23084180","type":"journal-article","created":{"date-parts":[[2022,4,10]],"date-time":"2022-04-10T23:06:01Z","timestamp":1649631961000},"page":"4180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Time Course of Changes in the Neurovascular Unit after Hypoxic-Ischemic Injury in Neonatal Rats"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1390-7715","authenticated-orcid":false,"given":"Kazuki","family":"Hatayama","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Women & Infants Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, RI 02905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sydney","family":"Riddick","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Women & Infants Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, RI 02905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fares","family":"Awa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Women & Infants Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, RI 02905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Women & Infants Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, RI 02905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Virgintino","sequence":"additional","affiliation":[{"name":"Human Anatomy and Histology Unit, Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari School of Medicine, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6532-7683","authenticated-orcid":false,"given":"Barbara","family":"Stonestreet","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Women & Infants Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, RI 02905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/jcbfm.2014.255","article-title":"Brain barrier properties and cerebral blood flow in neonatal mice exposed to cerebral hypoxia-ischemia","volume":"35","author":"Ek","year":"2015","journal-title":"J. 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