{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T13:18:51Z","timestamp":1769692731259,"version":"3.49.0"},"reference-count":105,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:00:00Z","timestamp":1606867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2R01HD057100"],"award-info":[{"award-number":["2R01HD057100"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R21NS095130"],"award-info":[{"award-number":["1R21NS095130"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R21NS096525"],"award-info":[{"award-number":["1R21NS096525"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R44 NS084575"],"award-info":[{"award-number":["R44 NS084575"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perinatal hypoxia-ischemia (HI) is a major cause of brain injury and mortality in neonates. Hypoxic-ischemic encephalopathy (HIE) predisposes infants to long-term cognitive deficits that influence their quality of life and place a large burden on society. The only approved treatment to protect the brain after HI is therapeutic hypothermia, which has limited effectiveness, a narrow therapeutic time window, and is not considered safe for treatment of premature infants. Alternative or adjunctive therapies are needed to improve outcomes of full-term and premature infants after exposure to HI. Inter-alpha inhibitor proteins (IAIPs) are immunomodulatory molecules that are proposed to limit the progression of neonatal inflammatory conditions, such as sepsis. Inflammation exacerbates neonatal HIE and suggests that IAIPs could attenuate HI-related brain injury and improve cognitive outcomes associated with HIE. Recent studies have shown that intraperitoneal treatment with IAIPs can decrease neuronal and non-neuronal cell death, attenuate glial responses and leukocyte invasion, and provide long-term behavioral benefits in neonatal rat models of HI-related brain injury. The present review summarizes these findings and outlines the remaining experimental analyses necessary to determine the clinical applicability of this promising neuroprotective treatment for neonatal HI-related brain injury.<\/jats:p>","DOI":"10.3390\/ijms21239193","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T07:49:54Z","timestamp":1606895394000},"page":"9193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Novel Neuroprotective Agents to Treat Neonatal Hypoxic-Ischemic Encephalopathy: Inter-Alpha Inhibitor Proteins"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3845-2953","authenticated-orcid":false,"given":"Liam M.","family":"Koehn","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The Alpert Medical School of Brown University, Women &amp; Infants Hospital of Rhode Island, Providence, RI 02905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Alpert Medical School of Brown University, Women &amp; Infants Hospital of Rhode Island, Providence, RI 02905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2534-2221","authenticated-orcid":false,"given":"Aric F.","family":"Logsdon","sequence":"additional","affiliation":[{"name":"Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA"},{"name":"Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2697-7963","authenticated-orcid":false,"given":"Yow-Pin","family":"Lim","sequence":"additional","affiliation":[{"name":"ProThera Biologics, Inc., Providence, RI 02903, USA"},{"name":"Department of Pathology and Laboratory Medicine, The Alpert Medical School of Brown University, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara S.","family":"Stonestreet","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Alpert Medical School of Brown University, Women &amp; Infants Hospital of Rhode Island, Providence, RI 02905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1242\/jeb.01064","article-title":"Hypoxia\u2013ischemia in the immature brain","volume":"207","author":"Vannucci","year":"2004","journal-title":"J. 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