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Effects of inter-alpha inhibitor proteins on brain injury after exposure of neonatal rats to severe hypoxia-ischemia
Hypoxic-ischemic (HI) brain injury is one of the most common neurological problems occurring in premature and full-term infants after perinatal complications. Hypothermia is the only treatment approved for HI encephalopathy in newborns. However, this treatment is only partially protective, cannot be...
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| Published in: | Experimental neurology 2020-12, Vol.334, p.113442-113442, Article 113442 |
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| creator | Schuffels, Stephanie Nakada, Sakura Wu, Yuqi Lim, Yow-Pin Chen, Xiaodi Stonestreet, Barbara S. |
| description | Hypoxic-ischemic (HI) brain injury is one of the most common neurological problems occurring in premature and full-term infants after perinatal complications. Hypothermia is the only treatment approved for HI encephalopathy in newborns. However, this treatment is only partially protective, cannot be used to treat premature infants, and has limited efficacy to treat severe HI encephalopathy. Inflammation contributes to the evolution of HI brain injury in neonates. Inter-alpha Inhibitor Proteins (IAIPs) are immunomodulatory proteins that have neuroprotective properties after exposure to moderate HI in neonatal rats. The objective of the current study was to determine the neuroprotective efficacy of treatment with IAIPs starting immediately after or with a delay of one hour after exposure to severe HI of 120 min duration. One hundred and forty-six 7-day-old rat pups were randomized to sham control, HI and immediate treatment with IAIPs (60 mg/kg) or placebo (PL), and sham, HI and delayed treatment with IAIPs or PL. IAIPs or PL were given at zero, 24, and 48 h after HI or 1, 24 and 48 h after HI. Total brain infarct volume was determined 72 h after exposure to HI. Treatment with IAIPs immediately after HI decreased (P |
| doi_str_mv | 10.1016/j.expneurol.2020.113442 |
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•Exogenous inter-alpha inhibitor proteins (IAIPs) reduce severe hypoxic-ischemic injury.•Exogenous IAIPs decrease hypoxic-ischemic infarction volumes in males and females.•IAIP treatment after a 1 h reduces hypoxic-ischemic infarction volumes in male rats.</description><identifier>ISSN: 0014-4886</identifier><identifier>EISSN: 1090-2430</identifier><identifier>DOI: 10.1016/j.expneurol.2020.113442</identifier><identifier>PMID: 32896573</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alpha-Globulins - administration & dosage ; Alpha-Globulins - metabolism ; Animals ; Animals, Newborn ; Brain Injuries - etiology ; Brain Injuries - metabolism ; Brain Injuries - prevention & control ; Brain injury ; Female ; Humans ; Hypoxia-ischemia ; Hypoxia-Ischemia, Brain - complications ; Hypoxia-Ischemia, Brain - drug therapy ; Hypoxia-Ischemia, Brain - metabolism ; Inter-alpha inhibitor proteins ; Male ; Neonatal rats ; Neuroprotection ; Neuroprotection - drug effects ; Neuroprotection - physiology ; Pregnancy ; Random Allocation ; Rats ; Rats, Wistar ; Severity of Illness Index ; Sex</subject><ispartof>Experimental neurology, 2020-12, Vol.334, p.113442-113442, Article 113442</ispartof><rights>2020 Elsevier Inc.</rights><rights>Copyright © 2020 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-9b309001f4b01fbd0217c08d26eaa6d00980bb76be4f884d01a3a09cfd94b2e93</citedby><cites>FETCH-LOGICAL-c475t-9b309001f4b01fbd0217c08d26eaa6d00980bb76be4f884d01a3a09cfd94b2e93</cites><orcidid>0000-0002-6532-7683</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32896573$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schuffels, Stephanie</creatorcontrib><creatorcontrib>Nakada, Sakura</creatorcontrib><creatorcontrib>Wu, Yuqi</creatorcontrib><creatorcontrib>Lim, Yow-Pin</creatorcontrib><creatorcontrib>Chen, Xiaodi</creatorcontrib><creatorcontrib>Stonestreet, Barbara S.</creatorcontrib><title>Effects of inter-alpha inhibitor proteins on brain injury after exposure of neonatal rats to severe hypoxia-ischemia</title><title>Experimental neurology</title><addtitle>Exp Neurol</addtitle><description>Hypoxic-ischemic (HI) brain injury is one of the most common neurological problems occurring in premature and full-term infants after perinatal complications. Hypothermia is the only treatment approved for HI encephalopathy in newborns. However, this treatment is only partially protective, cannot be used to treat premature infants, and has limited efficacy to treat severe HI encephalopathy. Inflammation contributes to the evolution of HI brain injury in neonates. Inter-alpha Inhibitor Proteins (IAIPs) are immunomodulatory proteins that have neuroprotective properties after exposure to moderate HI in neonatal rats. The objective of the current study was to determine the neuroprotective efficacy of treatment with IAIPs starting immediately after or with a delay of one hour after exposure to severe HI of 120 min duration. One hundred and forty-six 7-day-old rat pups were randomized to sham control, HI and immediate treatment with IAIPs (60 mg/kg) or placebo (PL), and sham, HI and delayed treatment with IAIPs or PL. IAIPs or PL were given at zero, 24, and 48 h after HI or 1, 24 and 48 h after HI. Total brain infarct volume was determined 72 h after exposure to HI. Treatment with IAIPs immediately after HI decreased (P < 0.05) infarct volumes by 58.0% and 44.5% in male and female neonatal rats, respectively. Delayed treatment with IAIPs after HI decreased (P < 0.05) infarct volumes by 23.7% in male, but not in female rats. We conclude that IAIPs exert neuroprotective effects even after exposure to severe HI in neonatal rats and appear to exhibit some sex-related differential effects.
•Exogenous inter-alpha inhibitor proteins (IAIPs) reduce severe hypoxic-ischemic injury.•Exogenous IAIPs decrease hypoxic-ischemic infarction volumes in males and females.•IAIP treatment after a 1 h reduces hypoxic-ischemic infarction volumes in male rats.</description><subject>Alpha-Globulins - administration & dosage</subject><subject>Alpha-Globulins - metabolism</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Brain Injuries - etiology</subject><subject>Brain Injuries - metabolism</subject><subject>Brain Injuries - prevention & control</subject><subject>Brain injury</subject><subject>Female</subject><subject>Humans</subject><subject>Hypoxia-ischemia</subject><subject>Hypoxia-Ischemia, Brain - complications</subject><subject>Hypoxia-Ischemia, Brain - drug therapy</subject><subject>Hypoxia-Ischemia, Brain - metabolism</subject><subject>Inter-alpha inhibitor proteins</subject><subject>Male</subject><subject>Neonatal rats</subject><subject>Neuroprotection</subject><subject>Neuroprotection - drug effects</subject><subject>Neuroprotection - physiology</subject><subject>Pregnancy</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Severity of Illness Index</subject><subject>Sex</subject><issn>0014-4886</issn><issn>1090-2430</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqFUU2P0zAQtRCILQt_AXLkkjJ2vEl8QVqtlg9pJS5wtuxkTFyldrCdavvvmapLBScutjXvzZt5foy947DlwNsPuy0-LgHXFOetAEFV3kgpnrENBwW1kA08ZxsALmvZ9-0Ve5XzDgCUFN1LdtWIXrU3XbNh5d45HEquoqt8KJhqMy-ToffkrS8xVUuKBX0gRqhsMj4QtlvTsTKO6BXtEfOa8CQQMAZTzFwlQ4olVhkPSNB0XOKjN7XPw4R7b16zF87MGd883dfsx6f773df6odvn7_e3T7Ug-xuSq1sQ2aAO2npsCMI3g3Qj6JFY9qR3PRgbddalK7v5QjcNAbU4EYlrUDVXLOPZ91ltXscBwwlmVkvye9NOupovP4XCX7SP-NBd60U0AIJvH8SSPHXirnoPXnAeTZkdc1aSAm9UqppidqdqUOKOSd0lzEc9CkzvdOXzPQpM33OjDrf_r3lpe9PSES4PROQ_urgMek8eAwDjj5RdnqM_r9DfgOHkrCE</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Schuffels, Stephanie</creator><creator>Nakada, Sakura</creator><creator>Wu, Yuqi</creator><creator>Lim, Yow-Pin</creator><creator>Chen, Xiaodi</creator><creator>Stonestreet, Barbara S.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6532-7683</orcidid></search><sort><creationdate>20201201</creationdate><title>Effects of inter-alpha inhibitor proteins on brain injury after exposure of neonatal rats to severe hypoxia-ischemia</title><author>Schuffels, Stephanie ; Nakada, Sakura ; Wu, Yuqi ; Lim, Yow-Pin ; Chen, Xiaodi ; Stonestreet, Barbara S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-9b309001f4b01fbd0217c08d26eaa6d00980bb76be4f884d01a3a09cfd94b2e93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alpha-Globulins - administration & dosage</topic><topic>Alpha-Globulins - metabolism</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Brain Injuries - etiology</topic><topic>Brain Injuries - metabolism</topic><topic>Brain Injuries - prevention & control</topic><topic>Brain injury</topic><topic>Female</topic><topic>Humans</topic><topic>Hypoxia-ischemia</topic><topic>Hypoxia-Ischemia, Brain - complications</topic><topic>Hypoxia-Ischemia, Brain - drug therapy</topic><topic>Hypoxia-Ischemia, Brain - metabolism</topic><topic>Inter-alpha inhibitor proteins</topic><topic>Male</topic><topic>Neonatal rats</topic><topic>Neuroprotection</topic><topic>Neuroprotection - drug effects</topic><topic>Neuroprotection - physiology</topic><topic>Pregnancy</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Severity of Illness Index</topic><topic>Sex</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schuffels, Stephanie</creatorcontrib><creatorcontrib>Nakada, Sakura</creatorcontrib><creatorcontrib>Wu, Yuqi</creatorcontrib><creatorcontrib>Lim, Yow-Pin</creatorcontrib><creatorcontrib>Chen, Xiaodi</creatorcontrib><creatorcontrib>Stonestreet, Barbara S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schuffels, Stephanie</au><au>Nakada, Sakura</au><au>Wu, Yuqi</au><au>Lim, Yow-Pin</au><au>Chen, Xiaodi</au><au>Stonestreet, Barbara S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of inter-alpha inhibitor proteins on brain injury after exposure of neonatal rats to severe hypoxia-ischemia</atitle><jtitle>Experimental neurology</jtitle><addtitle>Exp Neurol</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>334</volume><spage>113442</spage><epage>113442</epage><pages>113442-113442</pages><artnum>113442</artnum><issn>0014-4886</issn><eissn>1090-2430</eissn><abstract>Hypoxic-ischemic (HI) brain injury is one of the most common neurological problems occurring in premature and full-term infants after perinatal complications. Hypothermia is the only treatment approved for HI encephalopathy in newborns. However, this treatment is only partially protective, cannot be used to treat premature infants, and has limited efficacy to treat severe HI encephalopathy. Inflammation contributes to the evolution of HI brain injury in neonates. Inter-alpha Inhibitor Proteins (IAIPs) are immunomodulatory proteins that have neuroprotective properties after exposure to moderate HI in neonatal rats. The objective of the current study was to determine the neuroprotective efficacy of treatment with IAIPs starting immediately after or with a delay of one hour after exposure to severe HI of 120 min duration. One hundred and forty-six 7-day-old rat pups were randomized to sham control, HI and immediate treatment with IAIPs (60 mg/kg) or placebo (PL), and sham, HI and delayed treatment with IAIPs or PL. IAIPs or PL were given at zero, 24, and 48 h after HI or 1, 24 and 48 h after HI. Total brain infarct volume was determined 72 h after exposure to HI. Treatment with IAIPs immediately after HI decreased (P < 0.05) infarct volumes by 58.0% and 44.5% in male and female neonatal rats, respectively. Delayed treatment with IAIPs after HI decreased (P < 0.05) infarct volumes by 23.7% in male, but not in female rats. We conclude that IAIPs exert neuroprotective effects even after exposure to severe HI in neonatal rats and appear to exhibit some sex-related differential effects.
•Exogenous inter-alpha inhibitor proteins (IAIPs) reduce severe hypoxic-ischemic injury.•Exogenous IAIPs decrease hypoxic-ischemic infarction volumes in males and females.•IAIP treatment after a 1 h reduces hypoxic-ischemic infarction volumes in male rats.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32896573</pmid><doi>10.1016/j.expneurol.2020.113442</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-6532-7683</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Alpha-Globulins - administration & dosage Alpha-Globulins - metabolism Animals Animals, Newborn Brain Injuries - etiology Brain Injuries - metabolism Brain Injuries - prevention & control Brain injury Female Humans Hypoxia-ischemia Hypoxia-Ischemia, Brain - complications Hypoxia-Ischemia, Brain - drug therapy Hypoxia-Ischemia, Brain - metabolism Inter-alpha inhibitor proteins Male Neonatal rats Neuroprotection Neuroprotection - drug effects Neuroprotection - physiology Pregnancy Random Allocation Rats Rats, Wistar Severity of Illness Index Sex |
| title | Effects of inter-alpha inhibitor proteins on brain injury after exposure of neonatal rats to severe hypoxia-ischemia |
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