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This study examined the involvement of PARP\u20101 in ischemic brain injury in the 7\u2010day old rat, 0.5\u201348 h after unilateral carotid artery ligation and 2 h of 7.8% oxygen. This experimental paradigm produced a mild to moderate injury; 40\u201367% of animals in the ligated groups had histological evidence of neuronal death. Ipsilateral cortical injury was seen at all survival times, while mild contralateral cortical injury was seen only at the 1 h survival time. Hippocampal injury was delayed relative to the cortex and did not show a biphasic pattern. Immunohistochemical staining for PARP showed bilateral increased staining as early as 1 h post\u2010hypoxia. PARP staining at early time periods was most intense in layer V of cortex, but did not demonstrate a pattern of cell clusters or columns. Ipsilateral PARP\u20101 levels quantified by western blotting showed a biphasic pattern of elevation with peaks at 0.5 and 12 h post\u2010hypoxia. Contralateral PARP\u20101 levels were also elevated at 0.5 and 24 h. PARP activity as determined by immunoreactivity for poly(ADP\u2010ribose) (PAR) was increased ipsilaterally at 0.5, 2 and 12 h survival times. Cortical caspase 3\u2010activity was increased ipsilaterally at 6, 12, and 24 h and contralaterally at 0.5, 1, 2 and 6 h post\u2010hypoxia.<\/jats:p><jats:p>There are three main findings in this study. First, changes in the distribution and amount of cell death correlate well with measured PARP\u20101 levels after hypoxia\u2013ischemia, and both display biphasic characteristics. Second, there are significant early, transient morphological and biochemical changes in the contralateral cortex after neonatal hypoxia\u2013ischemia due to unilateral permanent occlusion of a carotid artery followed by 2 h of systemic hypoxia. Third, variability in the responses of individual pups to hypoxia\u2013ischemia suggests the presence of unidentified confounding factors.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.ijdevneu.2005.08.002","type":"journal-article","created":{"date-parts":[[2005,10,5]],"date-time":"2005-10-05T11:07:40Z","timestamp":1128510460000},"page":"673-686","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Biphasic changes in the levels of poly(ADP\u2010ribose) polymerase\u20101 and caspase 3 in the immature brain following hypoxia\u2013ischemia"],"prefix":"10.1002","volume":"23","author":[{"given":"Shannon S.","family":"Martin","sequence":"first","affiliation":[{"name":"University of Texas Medical Branch at Galveston USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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