{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:32:34Z","timestamp":1790976754725,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2008,7,24]],"date-time":"2008-07-24T00:00:00Z","timestamp":1216857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Perinatal hypoxia\u2013ischemia (HI) occurs in 0.2%\u20130.4% of all live births, with 100% O<jats:sub>2<\/jats:sub> resuscitation (HHI) remaining a standard clinical treatment. HI produces a broad spectrum of neuronal death phenotypes ranging from a more noninflammatory apoptotic death to a more inflammatory necrotic cell death that may be responsible for the broad spectrum of reported dysfunctional outcomes. However, the mechanisms that would account for this phenotypic spectrum of cell death are not fully understood. Here, we provide evidence that Bcl\u20102\u2010associated X protein (Bax) can shuttle to different subcellular compartments in response to HI, thus triggering the different organelle\u2010associated cell death signaling cascades resulting in cell death phenotype diversity. There was an early increase in intranuclear and total nuclear Bax protein levels followed by a later Bax redistribution to the mitochondria and endoplasmic reticulum (ER). Associated with the organelle\u2010specific Bax shuttling time course, there was an increase in nuclear phosphorylated p53, cytosolic cleaved caspase\u20103, and caspase\u201012. When HI\u2010treated P7 rats were resuscitated with 100% O<jats:sub>2<\/jats:sub> (HHI), there were increased lesion volumes as determined by T2\u2010weighted magnetic resonance imaging with no change in cortical apoptotic signaling compared with HI treatment alone. There was, however, increased inflammatory (cytosolic\u2010cleaved interleukin\u20101\u03b2) and necrotic (increased nuclear 55\u2010kDa\u2010cleaved PARP\u20101 [poly\u2010ADP\u2010ribose 1] and decreased nuclear HMGB1 [nuclear high\u2010mobility group box 1]) after HHI. Furthermore, HHI increased ER calpain activation and ER Bax protein levels compared with HI alone. These data suggest that 100% O<jats:sub>2<\/jats:sub> resuscitation increases Bax\u2010mediated activation of ER cell death signaling, inflammation, and lesion volume by increasing necrotic\u2010like cell death. In light of these findings, the use of 100% O<jats:sub>2<\/jats:sub> treatment for neonatal HI should be reevaluated. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.21795","type":"journal-article","created":{"date-parts":[[2008,7,24]],"date-time":"2008-07-24T21:57:22Z","timestamp":1216936642000},"page":"3584-3604","source":"Crossref","is-referenced-by-count":30,"title":["Bax shuttling after neonatal hypoxia\u2013ischemia: Hyperoxia effects"],"prefix":"10.1002","volume":"86","author":[{"given":"Martin B.","family":"Gill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Bockhorst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ponnada","family":"Narayana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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