{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T12:09:18Z","timestamp":1785499758531,"version":"3.56.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,10,16]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Neurological deficits in hypoxic\u2010ischemic encephalopathy, even with therapeutic hypothermia, are partially attributed to white matter injury. We theorized that proteasome insufficiency contributes to white matter injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Neonatal piglets received hypoxia\u2010ischemia (\n              <jats:styled-content style=\"fixed-case\">HI<\/jats:styled-content>\n              ) or sham procedure with normothermia, hypothermia, or hypothermia+rewarming. Some received a proteasome activator drug (oleuropein) or white matter\u2013targeted, virus\u2010mediated proteasome knockdown. We measured myelin oligodendrocyte glycoprotein, proteasome subunit 20S (P20S), proteasome activity, and carbonylated and ubiquitinated protein levels in white matter and cerebral cortex.\n              <jats:styled-content style=\"fixed-case\">HI<\/jats:styled-content>\n              reduced myelin oligodendrocyte glycoprotein levels regardless of temperature, and myelin oligodendrocyte glycoprotein loss was associated with increased ubiquitinated and carbonylated protein levels. Ubiquitinated and carbonyl\u2010damaged proteins increased in white matter 29\u00a0hours after\n              <jats:styled-content style=\"fixed-case\">HI<\/jats:styled-content>\n              during hypothermia to exceed levels at 6 to 20\u00a0hours. In cortex, ubiquitinated proteins decreased. Ubiquitinated and carbonylated protein accumulation coincided with lower P20S levels in white matter; P20S levels also decreased in cerebral cortex. However, proteasome activity in white matter lagged behind that in cortex 29\u00a0hours after\n              <jats:styled-content style=\"fixed-case\">HI<\/jats:styled-content>\n              during hypothermia. Systemic oleuropein enhanced white matter P20S and protected the myelin, whereas proteasome knockdown exacerbated myelin oligodendrocyte glycoprotein loss and ubiquitinated protein accumulation after\n              <jats:styled-content style=\"fixed-case\">HI<\/jats:styled-content>\n              . At the cellular level, temperature and\n              <jats:styled-content style=\"fixed-case\">HI<\/jats:styled-content>\n              interactively affected macroglial P20S enrichment in subcortical white matter. Rewarming alone increased macroglial P20S immunoreactivity, but this increase was blocked by\n              <jats:styled-content style=\"fixed-case\">HI<\/jats:styled-content>\n              .\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Oxidized and ubiquitinated proteins accumulate with\n              <jats:styled-content style=\"fixed-case\">HI<\/jats:styled-content>\n              \u2010induced white matter injury. Proteasome insufficiency may drive this injury. Hypothermia did not prevent myelin damage, protect the proteasome, or preserve oxidized and ubiquitinated protein clearance after\n              <jats:styled-content style=\"fixed-case\">HI<\/jats:styled-content>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.118.009415","type":"journal-article","created":{"date-parts":[[2018,10,3]],"date-time":"2018-10-03T09:01:59Z","timestamp":1538557319000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Proteasome Biology Is Compromised in White Matter After Asphyxic Cardiac Arrest in Neonatal Piglets"],"prefix":"10.1161","volume":"7","author":[{"given":"Polan T.","family":"Santos","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin E.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May W.","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Neonatology Department of Pediatrics Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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